To our best knowledge this is the first study to assess and compare lower limb biomechanics and gait pattern between patients undergoing total knee arthroplasty with use of fixed-bearing medial-pivot and multi-radius design implants. Results of this study show that there were no statistical differences between both types of implants and even though there was significant improvement in patient-reported outcome and gait pattern, those parameters still differ significantly in comparison to healthy volunteers. The problem with dissatisfaction after operative treatment may not lay in the procedure itself, but many different factors may contribute to it. Next studies comparing other designs of implants, as well as proper rehabilitation protocol should be performed

Background: Genetic factors are considered important risk factors for the occurrence of osteoarthritis (OA), which has received extensive attention. This study examined the research on the relationship between genetic factors and the pathogenesis of OA from a bibliometric perspective. Methods: We searched Web of Science Core Collection for original and review articles on genetic factors and OA. We used R package “bibliometrix” to perform statistical and visualization analysis of countries, institutions, authors, journals, and keywords. Results: A total of 1,127 articles met the inclusion criteria, with an average citation of 20.41 per article. From 2012 to 2022, the average annual growth rate of research in this field was 7.83%. The corresponding authors of the published articles were mainly from China, the USA, and the UK. Boston University emerged as the most active and important institution, while the Osteoarthritis and Cartilage published the most articles in this field. The keywords “polymorphism”, “genetic” and “mendelian randomization” indicate the future research directions. Conclusion: This bibliometric study provides an overview of the key topics and trends in genetic factors and OA pathogenesis research. The high-frequency keywords suggest the current and potential future focus of this field, involving methods, mechanisms, and populations.

Osteoarthritis (OA) is the most common cause of pain and disability in adults. Dietary supplements such as undenatured type II collagen (UC-II) have shown to have some benefits in OA treatment. This study aimed to assess changes in pain levels among knee OA patients treated with UC-II for 6 months. Patients with knee OA of any grade were given a daily 40 mg dose of UC-II (CondroArtil®) as a dietary supplement for 6 months. Pain levels were measured using the visual analog scale (VAS) before starting UC-II 6 months thereafter. A total of 100 patients (62/38: male/female) with a mean age of 46.3 ± 13.8 years participated in the study. Most patients (60%) had mild to moderate OA (grade I or II). The UC-II supplementation was shown to significantly reduce pain levels (p<0.001) with a negative correlation between pain reduction and age (p=0.006) and BMI (p=0.049). The OA severity also affected pain reduction (p=0.011), with grade II OA experiencing higher pain levels. Previous physical therapy and food supplements had a significant impact on pain reduction (p=0.017 and p=0.012, respectively). The study suggests that UC-II is an effective treatment for reducing pain in patients with knee OA.

Osteoarthritis (OA) has become one of the most common disabilities among elders, especially in female. Obesity and mechanical injury causing OA are attributed to joint loading, cartilage disintegration, bone loss and inflammation as well. Several strategies used for treatment OA including non-pharmacological and pharmacological. Fucoidan possesses several bioactivities such as antitumor, antiviral, anticoagulation, anti-obesity, and immunomodulation. This study aims to investigate the effect of fucoidan in surgery-induced OA on diet-induced obesity rats. OA was induced by anterior cruciate ligament transection and partial medial meniscectomy (ACLT+MMx). Male SD rats were fed high-fat diet (HFD) for 4 weeks to induce obesity before ACLT+MMx to induce OA. OA rats were administered with intragastric water or fucoidan in three different concentrations (32 mg/kg, 64 mg/kg, and 320 mg/kg) after the surgeries for 40 days with HFD. We observed that the swelling in knee joint was alleviated and hind paw weight distribution was rectified after feeding fucoidan, with no significant effect on weight gain and feed intake. Fucoidan administration indicated no significant variation on HDL-Cholesterol level, but reduced plasma triglycerides and LDL-Cholesterol level. In addition, weight-bearing tests showed improvement in the fucoidan-treated group. Our results suggested that fucoidan may improve meniscal/ligamentous injury and obesity-induced OA.

Pathological cleavage of collagen type II (Col2) and generation of Col2 neoepitopes can be good molecular markers of progression of osteoarthritis (OA). One of such potential biomarkers is collagen type II neoepitope C2C. The aim of this study was to correlate the degree of articular cartilage damage in OA patients with C2C expression in histological samples of tissues removed during total knee replacement. Cartilage samples were obtained from 27 patients aged from 55 to 66. In each patient medial and lateral tibia plateau samples were analyzed according to the OARSI histopathology grading system. C2C expression was evaluated on histological slides by semi-quantitative analysis using ImageJ Fiji software. Spearman´s rank correlation analysis showed significant positive correlation (rho=0.289, P=0.0356) between the histological grade of tissue damage and the percentage of C2C staining. In addition, highly significant positive correlation (rho=0.388, P=0.0041) was found between osteoarthritis score (combining the histological grade of damage with the OA macroscopic stage) and the percentage of C2C staining in the samples. The C2C expression was found in all the regions of the articular cartilage (i.e. the superficial zone, mid zone, deep zone and tidemark area and the zone of calcified cartilage). Our study suggests that local expression of C2C correlates with the cartilage damage in the knee affected by OA. This further assures that C2C can be a perspective marker for evaluation of pathological processes in OA course and OA clinical trials.

Knee osteoarthritis is the most popular type of osteoarthritis that causes extreme pain in elderly. Currently there is no cure for osteoarthritis. To lessen clinical symptoms, glucosamine was suggested. The primary goal of our study is to evaluate the efficacy and safety of glucosamine from recent studies. Electronic databases such as PubMed, Scopus, Cochrane were used to assess RCT. From the beginning through March 2023, the papers were checked, and if they fulfilled the inclusion criteria, they were then examined. WOMAC and VAS scales were considered as main outcome measure. A total of 15 studies were selected. Global pain was significantly decreased in comparison to placebo, as measured by the VAS index, with an overall effect size SMD of -7.41 ([95% CI] 14.31, 0.51). The WOMAC scale confirmed that pain, stiffness, and physical function had improved, however the effects were insufficient. A statistical update also revealed that there were no reports of serious medication interactions or significant adverse events. To summarize, glucosamine is more effective than a placebo at reducing pain in knee osteoarthritis patients. In long-term treatment, oral glucosamine sulfate 1500 mg/day is believed to be well tolerated.

Osteoarthritis of the hand (HOA) is one of the most common musculoskeletal diseases affecting health. Osteophytes, documented by imaging procedures are often used as diagnostic criteria. The gold standard is the radiographic image, however, more sensitive and saver methods such as ultrasound are gaining in importance. We investigated the prevalence, grade and pattern of osteophytes by high resolution ultrasound investigation (US) in a population-based cross-sectional study. Factory workers were recruited at work. 26 finger joints of each participant were examined with US with grading the occurrence of osteophytes in a semiquantitative score ranging 0-3, increasing scores indicated larger osteophytes. 427 participants (mean age 53.5 years, range. 20-79 years) were investigated, resulting in 11,000 scored joints. At least one osteophyte was found in 4,546/11,000 (41.3%) joints or 426/427 (99.8%) participants but grade 2 or 3 osteophytes were seen in only 553 (5.0%) joints. The number of os-teophyte sum score increased with age (0.18/year of age increase, p<0.001). Distal interphalange-al joints (DIP) were predominantly affected with 61%, followed by proximal interphalangeal joints (PIP) with 48%, carpometacarpal joint 1 (CMC1) with 39% and metacarpophalangeal joints (MCP) with 16%. In conclusion, US is a feasible screening tool for osteophytes and HOA. Grade 1 osteophytes are a common finding in the working population when assessed by ultrasound and their prevalence is increasing with age. Prevalence of grade 2 or 3 osteophytes is less common and reflects clini-cal presence of HOA. Follow up investigations are necessary to recognize the predictive rele-vance of early osteophytes.

Osteoarthritis (OA) is a debilitating degenerative joint disease that results in chronic pain and inflammation due to progressive mechanical and proteolytic cartilage degradation. Articular chondrocytes, the main cell type present in cartilage, are responsible for the deposition and maintenance of the cartilage extracellular matrix (ECM). However, following damage and inflammation, chondrocytes undergo hypertrophy, apoptosis, and contribute to inflammation and ECM degradation. NF-κB signaling is known to be dysregulated in OA. TRAPPC9, a vesicle trafficking protein, is known to directly activate NF-κB signaling in neuronal and bone cells, however, the biological significance of this protein in chondrocytes has yet to be elucidated. Here, we demonstrate that TRAPPC9 enhances pro-inflammatory gene and protein expression in murine primary articular chondrocytes. Furthermore, we show that TRAPPC9 elicits these responses via phosphorylation of P-100 that activates non-canonical NF-κB signaling. Taken together, these findings suggest TRAPPC9 may be a potential therapeutic target to decrease inflammation and matrix degradation during OA pathology.

Objectives The aim of this study was to measure the magnitude of forces in the joints of the lower limb whilst running barefoot and compare them to the forces generated whilst wearing running shoes with a thick midsole.MethodsTwenty-three volunteers who utilised running as their main sport or a training aid ran as training aid were included in this study. Each volunteer would run down a fourteen-meter-long corridor both barefoot and with running shoes. Forces for joints of the lower limb were collected using a Vicon motion analysis system and force plates. The joint forces for the ankles, knees and hips were taken as the largest joint force experienced during the stance phase and then averaged over five running trials.ResultsThere was significant reduction in the joint forces for the ankles, knees, and hips when barefoot running compared to the shod condition.ConclusionBarefoot running could be utilised to prevent both acute and degenerative injuries of the lower limb.

ABSTRACT: Understanding the basis of osteoarthritis (OA) has seen some interesting advancements in recent years. It has been observed that cartilage degeneration is preceded by subchondral bone lesions, suggesting a key role of this mechanism within the pathogenesis and progression of OA, including the formation of ectopic bone and osteophytes. Moreover, low-grade, chronic inflammation of the synovial lining has gained a central role in the definition of OA pathophysiology, and central immunological mechanisms, innate but also adaptive, are now considered crucial in driving inflammation and tissue destruction. In addition, the role of neuroinflammation and central sensitization mechanisms has been characterized as underlying causes of pain chronicity. This has led to a renewed definition of OA, which is now intended as a complex multifactorial joint pathology caused by inflammatory and metabolic factors underlying joint damage. Since this evidence can directly affect the definition of the correct therapeutic approach to OA, an improved understanding of these pathophysiological mechanisms is fundamental. This review provides an overview of the most updated evidence on OA pathogenesis; it presents the most recent insight on the pathophysiology of OA, describing the interplay between immunological and biochemical mechanisms proposed to drive inflammation and tissue destruction, as well as central sensitization mechanisms. Moreover, although the therapeutic implications consequent to the renewed definition of OA are beyond this review scope, some suggestions for intervention have been addressed.

Background: A Few preclinical studies have shown that Knee osteoarthritis (KOA) is linked to gut microbiome dysbiosis and chronic inflammation. This pilot study was designed to look at the gut microbiome composition in KOA patients and normal individuals with or without vitamin D deficiency (VDD, serum vitamin D <30 ng/ml). Methods: This pilot study was conducted prospectively in 24 participants. The faecal samples of all the participants were taken for DNA extraction. The V3-V4 region of 16s rRNA was amplified and the library was prepared and sequenced on the Illumina Miseq platform. Results: The mean (±SD) age was 45.5 (±10.2) years with no defined co-morbidities. Of 447 total Operational Taxonomic Units (OTUs), a differential abundance of 16 nominally significant OTUs between the groups were observed. Linear discriminate analysis (LEfSe) revealed a significant difference in bacteria among the study groups. Pseudobutyrivibrio and Odoribacter were specific for VDD while Parabacteroides, Butyricimonas, and Gordonibacter were abundant in the KOA_VDD group and Peptococcus, Intestimonas, Delftia, and Oribacterium were abundant in the KOA group. About 80% of bacterial species were common among different groups and hence labeled as core bacterial species. However, the core microbiome of KOA and VDD groups were not seen in the KOA_VDD group, suggesting that these bacterial groups were affected by the interaction of the KOA and VDD factors. Conclusion: Parabacteroides, Butyricimonas, Pseudobutyrivibrio, Odoribacter, and Gordonibacter are the predominant bacteria in vitamin D deficient patients with or without KOA. Together these results indicate an association between the gut microbiome, vitamin D, and knee osteoarthritis.

BACKGROUND: Knee osteoarthritis (OA) commonly causes increase in the patients’ disability and reduce their function because it causes pain, limitation in knee range of motion and decrease in muscle power.AIM: This study investigated the effect of three different physical therapy programs on knee range of motion , pain level, muscle strength and functional condition in patients with knee OA. DESIGN: Randomized comparative study.SETTING: Outpatient Rehabilitation clinic of Tongji Hospital (Wuhan, China).POPULATION: Seventy-two patients of Knee OA (aged 40-70) enrolled and randomly allocated into three groups. Group A (n=24) received physical agents and isometric quadriceps exercises, group B (n=24) received same physical agents as group A in addition to open kinetic chain exercises and group C (n=24) received physical agents as group A in addition to closed kinetic chain exercises.METHODS: knee range of motion (by electro goniometer), knee pain level (by VAS), quadriceps muscle strength (by isokinetic dynamometer) and functional condition (by WOMAC) were assessed before and after 5 weeks of treatment.RESULTS: In between group analysis, there were significant differences (P<0.05) between the three groups for all outcome measure. In within-group analysis, group C was the only group that showed significant differences (P<0.05) in all the outcomes. Group A and B showed significant differences (P<0.05) in quadriceps muscle strength and knee pain and no significant differences (P>0.05) in knee ROM and functional condition.CONCLUSIONS: After the study, our solid conclusion is that in physical therapy programs or protocols, closed kinematic chain exercise is very effective, it improves knee ROM, and help in reducing knee pain, muscle strength, function and disability for patients with knee osteoarthritis.CLINICAL REHABILITATION IMPACT: Comparison between different physical therapy programs provides the rehabilitation team with the best treatment intervention that is more effective in treating the problems associated with knee osteoarthritis.

Osteoarthritis (OA) is a joint disease involving cartilage degeneration. This study aimed to compare properties of chondrocytes from less-affected (LA-Cartilage) and severely-affected (SA-Cartilage) of human OA articular cartilage. Based on Dougados classification, OA cartilage was classified into two groups; less-affected (Grade 0–1) and severely-affected (Grade 2–3). Chondrocytes from each group were cultured until passage (P) 4. Growth, migration, stem cell properties and chondrogenic properties under normal and inflammatory conditions, and the formation of in vitro 3D cartilage tissues were compared between groups. The growth and migratory properties of LA-chondrocytes and SA-chondrocytes were similar, except that the migration rate of SA-chondrocytes was significantly higher at P0 compared to LA-chondrocytes. Both LA-chondrocytes and SA-chondrocytes expressed mesenchymal stem cell markers and tri-lineage differentiation, but the expression of stem cell markers decreased significantly with increasing passage number. Exposure to inflammatory conditions induced distinct morphological changes and significant increases in expression of SOX9 at P4 and MMP3 at P1 for LA-chondrocytes. LA-chondrocytes and SA-chondrocytes able to develop into in vitro 3D constructs, but SA-chondrocytes exhibited superior cartilage-like properties. Chondrocytes from both less- and severely-affected regions are suitable to be used in clinical applications, however, chondrocytes from severely-affected regions could be a more favorable cell source.

Chronic joint inflammatory disorders such as osteoarthritis and rheumatoid arthritis have in common an upsurge of inflammation, and oxidative stress, resulting in progressive histological alterations and disabling symptoms. Currently used conventional medication (ranging from pain-killers to biological agents) is potent, but frequently associated with serious, even life-threatening side effects. Used for millennia in traditional herbalism, medicinal plants are a promising alternative, with lower rate of adverse events and an efficiency frequently comparable with that of conventional drugs. Nevertheless, their mechanism of action is in many cases elusive and/or uncertain. Even many of them have been proved effective in studies done in vitro or on animal models, there is a scarcity of human clinical evidence. The purpose of this review is to summarise the available scientific information on these joint-friendly medicinal plants, which have been already tested in human studies: Arnica montana, Boswelliaspp., Curcuma spp., Equisetum arvense, Harpagophytumprocumbens, Salix spp., Sesamumindicum, Symphytumofficinalis, Zingiberofficinalis, Panaxnotoginseng, Whitaniasomnifera.

Background: Cardiovascular disease (CVD) increases the risk of mortality and morbidity in patients with rheumatoid arthritis (RA). Patients with RA have a 50-60% increased risk for CVD compared with the general population. Cardiovascular risk is commonly meas-ured using the Systemic Coronary Risk Estimation 2 calculator modified for patients with RA. Traditional modifiable risk factors for CVD include arterial hypertension, dyslipidemia, insulin resistance, diabetes, cigarette smoking, and low physical activity. In this study, we analyzed the effects of smoking and the risk of CVD in patients with RA. Methods: This was a prospective, clinical, cohort study with an eight-year follow-up pe-riod. A total of 201 patients, 124 with RA (study group) and 77 with osteoarthritis (OA) (control group), were included in this study. However, only 137 patients (82 with RA and 55 with OA) completed the study. Fifty-eight patients (41 with RA and 17 with OA) died during the study period. We compared the prevalence of smoking and its association with the risk for CVD and RA. Results: The prevalence of smoking in the RA group was higher than that in the OA group (p<0.0001). Trends in the prevalence of smoking in both groups did not change signifi-cantly during the follow-up period. In the RA group, smoking was associated with the in-cidence of CVD in current smokers (p=0.028) and in patients with a history of smoking (p=0.016). These results suggest that smokers have an increased risk for RA. The trend of continued smoking in patients with RA may be attributed to attempts to reduce stress caused by RA symptoms. Conclusions: Previous studies have shown that current and former smokers with RA have more severe symptoms, more joint damage, and poorer response to therapy than those who have never smoked. However, the reason underlying the trend of continued cigarette smoking in patients with RA remains unclear. Further studies are needed to clarify the trend of continued smoking in patients with RA.

The primary objective of this study is to report the initial efficacy data observed with the use of cryopreserved human umbilical tissue allograft for the supplementation of cartilage defects in patients with symptomatic knee osteoarthritis. Our primary endpoints were pain, stiffness, and functional recovery scores. In this ongoing study, 55 participants (age 56-93 years) received a single Wharton's jelly tissue allograft application. The study dose consisted of 150mg of Wharton's jelly allograft suspended in approximately 2mL of sterile Sodium Chloride 0.9% solution (normal saline). Each study knee application was performed under ultrasound guidance in a physician's office. The research methodology consisted of NPRS scores and WOMAC subsection scores including pain, stiffness, and physical function. Study enrollment consisted of 55 patients followed for a post-application duration of 90 days. No adverse events or adverse reactions were reported. The results demonstrated statistically significant improvements of NPRS and WOMAC in initial versus 90-day examination. The data represents Wharton's jelly tissue allograft applications are a safe, non-surgical, and efficacious for patients with symptomatic articular cartilage defects associated with osteoarthritis of the knee. 

The African bush and forest elephants, Loxodonta Africana and Loxodonta cyclotis, and the Asian elephant, Elephas maximus, are the largest land-dwelling animals. Elephants need to be highly mobile and active in order to find fresh food and water, and in the case of males, to locate females in estrus for breeding. Asian elephants walk up to 21 km each day and African elephants can walk up to 28 km per day. This high level of mobility in the wild is also important for maintaining an optimum musculoskeletal health. However, most zoo elephants live in restricted spaces and cold climates that require extended periods of indoor confinement are therefore unable to be as physically active. Zoo enclosures for elephants are relatively small with hard surfaces (i.e. concrete, tarmac and hard packed dirt), so they cannot exercise and are forced to stand on unnaturally hard surfaces continually. Physical inactivity in captivity makes them more prone to gaining weight and developing bone and joint diseases such as osteomyelitis, joint ankylosis and osteoarthritis (OA). Many health and welfare problems in captive elephants are likely to be caused by the lack of mobility. This perspective article focuses on the possible link between captivity, mobility, physical inactivity and the development of OA in captive elephants.

Osteoarthritis and rheumatoid arthritis are common cartilage and joint diseases that globally affect more than 200 and 20 million people, respectively. Several transcription factors have been implicated in the onset and progression of osteoarthritis, including Runx2, C/EBPβ, HIF2α, Sox4, and Sox11. IL-1β also leads to osteoarthritis through NF-ĸB, IκBζ, and Zn²⁺-ZIP8-MTF1 axis. IL-1, IL-6, and TNFα play a major pathological role in rheumatoid arthritis through NF-ĸB and JAK/STAT pathways. Indeed, inhibitory reagents for IL-1, IL-6, and TNFα provide clinical benefits for rheumatoid arthritis patients. Several growth factors, such as BMP, FGF, PTHrP, and Indian hedgehog, play roles regulating chondrocyte proliferation and differentiation. Disruption and excess of these signaling cause genetic disorders in cartilage and skeletal tissues. FOP, an autosomal genetic disorder characterized by ectopic ossification, is induced by mutant ACVR1. mTOR inhibitors were found to prevent ectopic ossification by ACVR1 mutations. ACH and related diseases are autosomal genetic diseases, which manifest severe dwarfism. CNP is currently the most promising therapy for ACH. In these ways, investigation of cartilage and chondrocyte diseases at molecular and cellular levels sheds light on the development of effective therapies. Thus, identification of signaling pathways and transcription factors implicated in these diseases is important.

Osteoarthritis (OA) is a disease that currently has no cure. There are numerous studies showing that carnosine and hyaluronic acid (HA) have a positive pharmacological action during joint inflammation. For this reason, the goal of this research was to discover the protective effect of a new HA+Carnosine formulation (FidHycarn) on the inflammatory response and on the cartilage degradation in in vivo experimental model of OA. This model was induced by a single intra-articular (i.ar.) injection of 25µl normal saline having 1mg of monosodium iodoacetate solution (MIA) in the knee joint. MIA injection caused histological alterations and degradation of cartilage as well as behavioral changes. Oral treatment with FidHycarn ameliorated the macroscopic signs, improved thermal hyperalgesia and weight distribution of hind paw as well as decreased histological and radiographic alterations. The oxidative damage was analyzed by evaluating the levels of nitrotyrosine and inducible nitric oxide synthase (iNOS) that were significantly reduced in FidHycarn rats. Moreover, the levels of pro-inflammatory cytokines and chemokines were also significantly reduced by FidHycarn. However, interestingly, in more cases, the effects of FidHycarn were not statistically different to Naproxen used as positive control. Thus, the new formulation containing Carnosine and HA could represent an interesting therapeutic strategy to combat osteoarthritis.

Background: Osteoarthritis is the most common degenerative joint disease resulting in pain and altered joint function. Objective: We investigated the possible association between serum interleukin-6 and symptoms of knee osteoarthritis with regard to pain, stiffness, physical function, assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). We also examined the connections between serum interleukin-6 and radiographic severity in primary knee osteoarthritis patients. Methods: In this case-control study, fifty primary knee osteoarthritis patients and fifty age and sex matched controls were randomly recruited. Serum interleukin-6 levels were immunoassayed in patients’ and controls’ serum. Patients’ knee pain, stiffness and physical function were assessed by the respective subscales of the WOMAC Index. Standing anteroposterior radiographs of the knee joint were performed and graded with the Kellegren-Lawrence grade. Results: The mean serum IL-6 level was significantly higher in osteoarthritis patients (110.22 ± 46.98pg/ml) than controls (46.04 ± 12.34 pg/ml) (p=0.001). The WOMAC Index in patients ranged from 0 – 95 and the Kellegren-Lawrence score mean was 2.7 ± 0.76. There was a significant correlation between serum IL-6 levels and pain (r=0.595 p=0.001), physical function score (r=0.666, p=0.001)), and the radiographic score (r=0.799, p=0.001). Regression analysis showed that IL-6 level had a greater impact on both the WOMAC Index (p=0.005) and the Kellegren-Lawrence score (p=0.01). Conclusion: Serum IL-6 level is increased in primary knee osteoarthritis patients. Also, serum interlukin-6 is significantly related to osteoarthritis symptoms and radiographic severity.

BackgroundAdvanced radiological stage of knee osteoarthritis (OA) and obesity are predictive of poorer and shorter response to viscosupplementation, but very few is known regarding the impact of other factors such as sport practice, comorbidities or anatomical features of OA. ObjectivesTo investigate the patient’s and OA characteristics associated with the duration of effectiveness (DE) of viscosupplementation in patients with knee OA.MethodsCross-sectional single center trial in patients with knee OA treated with intra-articular (IA) hyaluronic acid (HA) injection(s) within the previous 3 years. The investigator collected demographic and radiographic data (Kellgren grade, involved knee compartments), dosing regimen (single or repeat injections), presence and volume of joint effusion, previous or concomitant IA corticosteroid injection, number of previous viscosupplémentations and the comorbidities. The patient completed a questionnaire including the self-assessment of DE (number of weeks during which viscosupplementation was effective on symptoms), the activity level (sedentary, active, athletic), the level of sport activity (light, moderate or intensive). Predictors of DE were studied in univariate and multivariate analyses ResultsOne hundred five patients (149 knees) were analyzed (62% women, mean age 66.1 ± 13.2 years, mean BMI 27.5 ± 7.5 kg/m²). The mean DE was 48.2 + 24.8 weeks. In a bivariate analysis, the predictors of a shorter with DE were BMI >27.5kg/m2, more than 3 previous viscosupplémentations, Kellgren grade 4, sedentary patients, and more than 1 affected compartment. In the multivariate analysis, 4 independent factors remained associated with a shorter DE: BMI >27.5 kg/m2, knee multi-compartment damage, number of viscosupplements >3, sedentary lifestyle. A statistically significant association between a longer DE and treated arterial hypertension was found suggesting a beneficial effect of certain antihypertensive drugs. ConclusionThe study confirms the harmful influence of an increased BMI, It also shows that viscosupplementation is more effective in unicompartmental OA. Other points worth highlighting are the reduction in the duration of efficacy with repeated cycles of injections and the benefit of a regular physical activity.

Biomechanical changes such as increased knee adduction moment (KAM) during walking are known to be involved in the development and severity of knee osteoarthritis (OA). Although various foot progression angle (FPA) modifications during gait have been applied to reduce peak KAM, few studies have investigated effects of applying toe-in or toe-out walking modifications for knee OA on peak KAM and three-dimensional (3D) moments of the ankle joint. Kinetic moment variables were acquired from 35 individuals with medial knee compartment OA. A 3D motion analysis system and two force platforms were used to acquire KAM and 3D moments of both ankle joints during gait. Visual3D motion analysis program was used to obtain final moment data for statistical processing. Repeated-measures analysis of variance with Bonferroni adjustment was used to compare kinetic and kinematic values for each FPA walking condition. The first peak KAM of an internal rotation foot position of the FPA walking condition showed significant decrease compared to normal foot position walking (p &lt; 0.01). The second peak KAM of an external rotation foot position walking showed significant decrease compared to normal foot position walking (p &lt; 0.01). Compared to a normal foot position, peak ankle inversion moment of the external rotation foot position walking showed a significantly decrease (p &lt; 0.05). There were no interactive effects between FPA condition and limb sides for any KAM values (p &gt; 0.05). These results suggest that clinical application of toe-in or toe-out gait modification walking in individuals with knee OA should be performed based on biomechanical evaluations such as peak KAM.

The osteoarthritis (OA), the main cause of disability, is a chronic condition that most frequently affects older adults. As the population ages, the cost of treatment is placing pressure on the healthcare budget. As a result, it is imperative to evaluate the medicines' cost-effectiveness and the influence they have on health resource allocation. Hence, our study aims to summarize the cost and outcome of utilizing glucosamine in OA treatment. Authentic databases like Medline, Cochrane, and Scopus were adopted for the identification process up until July 2023. Our primary inclusion criteria centered on the economic evaluation of Glucosamine in OA treatments with provided the incremental cost-effectiveness ratio (ICER) at least. The Quality of Health Economic Studies (QHES) instrument was applied to grade the quality of the studies. A total of 7 qualified studies were selected and discussed the cost-effectiveness of glucosamine with or without other formulations. All of them demonstrated that glucosamine was cost-effective. There was an in-creasement of QALY when incorporating Glucosamine into conventional care. Moreover, Crystalline Glucosamine Sulfate (pCGS) was more cost-effective than the Other Formulations of Glucosamine (OFG). In overall, utilizing pCGS was more beneficial than OFG in terms both of cost and quality of life.

A two-year-old male Pomeranian dog visited the hospital due to side effects of surgical correction for patellar luxation. Stifle joint arthrodesis (SJA) was performed on the patient’s right leg using autologous bone grafting techniques. The right leg’s femur and tibial joint were angled 120-130◦ and the SJA plate was fixed on the front of the two bones. After performing joint fusion of the right limb, medial patellar luxation (MPL)-corrective surgery was performed to cut the tibial tuberosity on the left leg and the fixing force was increased using the figure-of-eight tension band wiring technique. The results were observed for walking and trotting of the right hind limb, evaluated for 27 days after surgery. It was difficult for the patient to walk because weight loading was not performed for 3 days after surgery; short strides and partial weight bearing were possible 5 to 7 days after surgery. After 10 days, the patient was able to move while bearing weight with a slight disruption. For trotting, the patient showed intermittent normal steps 5 to 7 days after surgery, but the disruption continued. After 14 days, trotting was possible and movements were shown to be maintained during everyday activities.

This study aimed to clarify the relationship between the joint and ligament structures of the subtalar joint and degeneration of the subtalar articular facet. We examined 50 feet from 25 Japanese cadavers. The number of articular facets, joint congruence, and intersecting angle were measured for the joint structure of the subtalar joint, and the footprint areas of the ligament attachments of the cervical ligament, interosseous talocalcaneal ligament (ITCL), and anterior capsular ligament were measured for the ligament structure. Also, subtalar joint facets were classified into Degeneration (+) and (-) groups according to degeneration of the talus and calcaneus. No significant relationship was identified between the joint structure of the subtalar joint and degeneration of the subtalar articular facet. In contrast, footprint area of the ITCL was significantly higher in the Degeneration (+) group than in the Degeneration (-) group for the subtalar joint facet. These results suggest that the joint structure of the subtalar joint may not affect degeneration of the subtalar articular facet. Degeneration of the subtalar articular facet may be related to the size of the ITCL.

(1) Background:A BMI &gt; 25 is the most decisive, albeit modifiable,risk factors for knee osteoarthritis (OA). This study aimed at assessing the efficacy of intra-articular injections of hybrid hyaluronic acid (HA) complexes (Synovial® H-L)for the treatment of kneeOA in overweight patientsin terms ofdisease severity, cardiocirculatory capacity, and quality of life. (2) Materials: In this single-site, open-label, prospective trial, 37 patients with symptomatic knee OA were assessed at baseline and 3 months after ultrasound-guided intra-articular injection of hybrid HA complexes (Synovial® H-L). (3) Results: Primary variables displaying a statistically significant improvement after treatment were pain (NRS), disease severity (WOMAC), and cardiopulmonary capacity a(6-Minute Walk Test). Among secondary variables, quality of life (SF-12) improved significantly, as did analgesic intake for pain control. No statistically significant difference was observed in body fat and muscle mass percentage measured by bioelectrical impedance analysis. (4) Conclusions:Intra-articular hybrid HA injections are significantly effective in improving OA-related disease severity, cardiopulmonary function, and analgesic intake. This supports the role of hybrid HA viscosupplementation as a non-pharmacological treatment to relieve pain, reduce disability and improve quality of life, and limit the risk of polypharmacy in overweight patients with knee OA.

Subchondral bone loss is an important pathological feature of early-stage temporomandibular joint (TMJ) osteoarthritis (OA). Previous studies focused mainly on the bone resorption by osteoclasts in early-stage OA, but the bone formation feature has not drawn enough attention. Sema4D/Plexin-B1 is a pair of molecules expressed by osteoclast/osteoblast, which is capable of inhibiting bone formation by osteoblasts. The present study found that subchondral bone loss in early-stage TMJ OA was accompanied by up-regulated expression of Sema4D in cartilage and subchondral bone and Plexin-B1 in subchondral bone. Reducing Sema4D level could inhibit the subchondral bone loss and cartilage degeneration of early-stage TMJ OA. In vitro, results revealed that Sema4D could reduce the expression of osteocalcin (OCN) and alkaline phosphatase (ALP), and increase the migrating capability of Plexin-B1-positive osteoblasts. Our results revealed that elevated Sema4D expression in early-stage TMJ OA might decrease the bone formation activity of osteoblasts in the subchondral bone by binding to Plexin-B1 expressed by osteoblasts. Inhibiting Sema4D/Plexin-B1 signaling in the early-stage OA holds promise as a strategy for new therapeutic approaches to osteoarthritis.

Glucosamine is the most common nutrition supplement used in the United States. It is promoted not only as a pain reliever but also a therapy to slow osteoarthritis. Although studies with 3,800 patients with osteoarthritis of the knee or hip found that glucosamine was no better than placebo, it continues to be used for these two indications due to its perceived safety. However, reports of an increased intraocular pressure are alarming, especially in glaucoma. Glycosaminoglycans play a key role in the physiology of the cornea, conventional outflow of aqueous humor and the retina. In theory, long-term treatment with glucosamine could reach a concentration that impacts the morphology and function of ocular tissues. We recommend ophthalmologists counsel glaucoma patients about the potential risks of glucosamine and encourage cessation in uncontrolled intraocular pressure.

As a chronic disease, osteoarthritis (OA) leads to degradation of both cartilage and subchondral bone, of which the development is related to proinflammatory cytokines like interleukin-1β. In the present study, the anti-inflammatory effect of Specnvezhenide in osteoarthritis and mechanism of it was studied in vitro and in vivo. The results showed that Specnvezhenide decreases interleukin-1β-induced expression of matix-degrading enzymes and reduces the activation of NF-κB and wnt/β-catenin pathways in vitro. Furthermore, Specnvezhenide treatment prevents the degeneration of both cartilage and subchondral bone in rats OA model. As conclusion, to the best of our knowledge, we report firstly that Specnvezhenide decreases interleukin-1β-induced inflammation on rat chondrocytes by inhibiting activation of NF-κB and wnt/β-catenin pathways, and has therapeutic potential in OA treatment.

Study of alterations in Osteoarthritis (OA) of Glypicans 1 to 6 (GPCs) and Notum in plasma, bone marrow mesenchymal stromal cells (BM-MSCs) and osteoblasts. Plasma levels of GPCs and Notum were measured of 25 patients and 24 healthy subjects. In addition, BM-MSCs from eight OA patients and eight healthy donors were cultured during 21 days with culture me-dium and osteogenic medium. Protein and gene expression levels of GPCs and Notum were de-termined by ELISA and qPCR at 0, 7 ,14 and 21 days. GPC5 and Notum have been found de-creased in OA patients’ plasma. OA BM-MSCs showed downexpression of GPC6 and upregula-tion of Notum. A decrease in GPC5 and Notum proteins and an increase in GPC3 were found. During osteogenic differentiation, elevated GPC2, 4, 5, 6 and Notum mRNA levels and decreased GPC3 were observed in OA. Furthermore, the protein levels of GPC2, GPC5 and Notum de-creased and GPC3 increased. Glypicans and Notum are altered in BM-MSCs and during osteo-genic differentiation from patients with OA. Furthermore, GPC5 and Notum can be proposed as new biomarkers of the pathology. The alterations found indicate that Notum could be a prom-ising therapeutic strategy for Osteoarthritis.

Osteoarthritis (OA) is the degeneration of cartilage in joints that results in bones rubbing against each other, it causes uncomfortable symptoms such as pain, swelling, stiffness, and can lead to disability. It usually occurs in the elderly and causes a large medical burden. The aim of this study is to evaluate cost-effectiveness between the standard treatment for osteoarthritis and the standard treatment with added crystalline glucosamine sulfate at various stages. The Markov analysis modelling was applied to evaluate the effect of both adding glucosamine compared to standard treatment from a societal perspective during whole patients’ lifetimes. Data input was collected by review in previous studies. The outcome was measured in quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) from a societal perspective was ap-plied with 3%-discounted for all cost and outcome. One-way analysis via Tornado diagram was performed to investigate the change of factors in model. In general, the adding glucosamine into the standard treatment proved to be more cost-effectiveness compared to the standard treatment. Particularly, early stage adding glucosamine in the treatment was cost-effectiveness then post-stage adding glucosamine. The addition of supplementing crystalline glucosamine sulfate to whole regimen at any stage was cost-effectiveness at willingness-to-pay (WTP) threshold

Osteoarthritis (OA) is the most common degenerative joint disease that causes chronic pain and disability. Different innate immune components, including macrophages, T cells, and neutrophils, participate in osteoarthritis pathophysiology. Neutrophils are the most abundant circulating leukocytes with multiple specialized functions contributing to innate and adaptive immune functions. Although neutrophils produce proinflammatory cytokines and chemokines, reactive oxygen species (ROS), matrix-degrading enzymes, and neutrophil extracellular traps (NET) that promote joint degradation as the first recruit cells in an inflamed joint, these cells also play an important role in joint repair by regulating the immune response, releasing anti-inflammatory factors, and activating some protective genes. In this review, various aspects of neutrophil biology, their role in inflammation and its association with osteoarthritis, and possible therapeutic approaches to target neutrophils for the treatment of osteoarthritis are described. Understanding neutrophil heterogeneity and their mechanisms of action in joint inflammation, provides a potential strategy for OA management.

Background: Conclusions of meta-analyses of clinical studies may substantially influence opinions of perspective patients and stakeholders in health care. Nineteen meta-analyses of clinical studies on the management of primary knee osteoarthritis (pkOA) with stem cells, published between January 2020 and July 2021, came to inconsistent conclusions regarding the efficacy of this treatment modality. It is possible that a separate meta-analysis based on an independent, systematic assessment of clinical studies on the management of pkOA with stem cells may reach a different conclusion. Methods: PubMed, Web of Science and the Cochrane library were systematically searched for clinical studies and meta-analyses of clinical studies on the management of pkOA with stem cells. All clinical studies and meta-analyses identified were evaluated in detail, as were all sub-analyses included in the meta-analyses. Results: The inconsistent conclusions regarding the efficacy of treating pkOA with stem cells in the 19 assessed meta-analyses were most probably based on substantial differences in literature search strategies among different authors, misconceptions about meta-analyses themselves, and misconceptions about the biology of stem cells. An independent, systematic review of the literature yielded a total of 183 studies, of which 33 were randomized clinical trials, including a total of 6860 patients with pkOA. However, it was not possible to perform a scientifically sound meta-analysis. Conclusion: Clinicians should interpret the results of the 19 assessed meta-analyses of clinical studies on the management of pkOA with stem cells with caution, and should be cautious of the conclusions drawn therein. Clinicians and researchers should strive to participate in FDA and/or EMA reviewed and approved clinical trials to provide clinically and statistically valid efficacy.

Osteoarthritis and rheumatoid arthritis are two of the most common chronic inflammatory joint diseases, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. The pathology of both osteoarthritis and rheumatoid arthritis involves multiple tissues within the joint, including the synovial joint lining and the bone, as well as the articular cartilage in osteoarthritis. In this review, we discuss the potential for the development of oligonucleotide therapies for these disorders by examining the evidence that oligonucleotides can modulate the key cellular pathways that drive the pathology of the inflammatory diseased joint pathology as well as evidence in preclinical in vivo models that oligonucleotides can modify disease progression.

Background: Aging is commonly accepted as a time period of declining heath. Aims: This review aimed to examine the research base concerning the use of term ‘successful aging’, a process and outcome deemed desirable, but challenging to attain. A second was to provide related information to demonstrate how health professionals as well as individuals can aim for a ‘successful aging’ process and outcome, despite the presence of disabling osteoarthritis. Methods: Information specifically focusing on ‘successful aging’ and the concept of improving opportunities for advancing ‘successful aging’ despite osteoarthritis was sought. Results: Among the many articles on ‘successful aging’, several authors highlight the need to include, a broader array of older adults into the conceptual framework. Moreover, conditions such as osteoarthritis should not necessarily preclude the individual from attaining a personally valued successful aging outcome. Conclusion: Pursuing more inclusive research and research designs, and not neglecting to include people with chronic osteoarthritis can potentially heighten the life quality of all aging individuals, while reducing pain and depression, among other adverse aging and disability correlates among those with osteoarthritis

Osteoarthritis (OA) is a common joint disorder found mostly in elderly people. The role of mechanical behavior in the progression of OA is complex and remains unclear. The stress-relaxation behavior of human articular cartilage in clinically defined osteoarthritic stages may have importance in diagnosis and prognosis of OA. In this study we investigated differences in the biomechanical responses among human cartilage of ICRS grades I, II and III using polymer dynamics theory. We collected 24 explants of human articular cartilage (eight each of ICRS grade I, II and III) and acquired stress-relaxation data applying a continuous load on the articular surface of each cartilage explant for 1180 s. We observed a significant decrease in Young’s modulus, stress-relaxation time, and stretching exponent in advanced stages of OA (ICRS grade III). The stretch exponential model indicated that significant loss in hyaluronic acid polymer might be the reason for the loss of proteoglycan in advanced OA. This work encourages further biomechanical modelling of osteoarthritic cartilage utilizing these data as input parameters to enhance the fidelity of computational models aimed at revealing how mechanical behaviors play a role in pathogenesis of OA.

Cartilage degeneration is a characteristic of osteoarthritis (OA) which is often observed in aging populations. This degeneration is due to the breakdown of articular cartilage (AC) mechanical and tribological properties, primarily attributed to lubrication failure. Understanding the reasons behind these failures and identifying potential solutions could have significant economic and societal implications, ultimately enhancing the quality of life. This review provides an overview of developments in the field of AC, focusing on its mechanical and tribological properties. The emphasis is on the role of lubrication in degraded AC, offering insights into its structure and function relationship. Further it explores the fundamental connection between AC mechano-tribological properties and the advancement of its degradation and puts forth recommendations for strategies to boost its lubrication efficiency.

The ultrasound guided viscosupplementation of the hip joint with hyaluronic acid(HA)is considered a standard procedure among the conservative treatments for hip arthritis.The aim of the study was to evaluate the clinical benefit and the incidence of adverse events of the technique in a obseravtional study at one year follow up. We evaluated a consecutive series of 85 patients with a diagnosis of symptomatic arthritis that performed intra-articular ultrasound-guided hyaluronic acid injections. The scales used for evaluation were modified Harris Hip Score(mHHS),WOMAC (Western Ontario and McMaster University),Hip Outcome Score (HOOS) with subscale Sport (HOOSs), for pain the Visual Analogic Scale (VAS).The patients were classified according to Tonnis’ radiological classification of arthrosis (range 0-3):20 patients(grade 0),32(grade 1),18(grade 2),15(grade 3).At last follow up all the scales increased:mHHS from 59.35 to 82.1,HOOS from 69.45 to 78.53,HOS Sport from 47.4 to 58.11,VAS from 6.09 to 3.97,WOMAC from 33.2 to 31.5 (p<0.05 for all the parameters);13/85 requested arthroplasty. Based on our findings, indication for use of hyaluronic acid is limited to patients with mild to moderate arthritis.Patients in advanced arthritis refusing replacement surgery and asking for this treatment should be informed about the poor results of the technique even in the short term follow up.

Glycosphingolipids (GSLs), a subtype of glycolipids containing sphingosine, are critical components of vertebrate plasma membranes, playing a pivotal role in cellular signaling and interactions. In human articular cartilage in osteoarthritis (OA), GSL expression is known notably to decrease. This review focuses on the roles of gangliosides, a specific type of GSL, in cartilage degeneration and regeneration, emphasizing their regulatory function in signal transduction. The expression of gangliosides, whether endogenous or augmented exogenously, is regulated at the enzymatic level, targeting specific glycosyltransferases. This regulation has significant implications for the composition of cell surface gangliosides and their impact on signal transduction in chondrocytes and progenitor cells. Different levels of ganglioside expression can influence signaling pathways in various ways, potentially affecting cell properties, including malignancy. Moreover, gene manipulations against gangliosides have been shown to regulate cartilage metabolism and chondrocyte differentiation in vivo and in vitro. This review highlights the potential of targeting gangliosides in the development of therapeutic strategies for osteoarthritis and cartilage injury and addresses promising directions for future research and treatment.

Background and Objectives: Knee osteoarthritis (KOA) is a degenerative disease that is targeting continuously people of different ages, but especially the elderly population, the number of which tends to increase continuously at the global level. Apart from age, excess weight can influence the evolution of the disease, with obesity being associated with a weak inflammation stage, and an imbalance between pro-inflammatory and anti-inflammatory cytokines. The present work aimed to identify specific biomarkers alike ACRP-30, IL-10, TNF-α, and IL-6 in synovial fluid and correlate them with patients’ clinical data. Materials and Methods: 24 subjects with KOA and over 50 years of age are involved in the present study. All patients performed a supine X-ray at the target knee. Ultrasound was performed using an ESAOTE MyLab Omega (ESAOTE Spa, Italy) ultrasound device and a 6-19 MHz linear array transducer. Results: The obtained results highlighted a significant correlation between age and adiponectin level (p=0.0451, r=-0.412). Also, the IL-10 values are lower in cases where the intensity of the pain is more pronounced (p=0.0405, r=-0.421). In addition, analyzing the data by gender, it was observed that in the case of males, stiffness is more related to age (p=0.0079, r=0.7993), compared to women (p=0.0203, r=0.6223). In the case of women, the progression of the disease tends to increase more intensively total WOMAC score’s values (p=0.00031, r=0.8342), compared with men (p=0.0289, r=7013). Regarding interleukins and BMI, significant correlations were observed only in the case of men. Conclusions: A significant correlation between age and adiponectin, and adiponectin and IL-6, suggests that advanced age may contribute to adiponectin reduction. Comparing men with women, it was observed that men's age is more related to rigidity, and IL-6 and IL-10 are directly correlated to BMI and women seem to be more sensitive to pain and stiffness.

In osteoarthritis (OA), oxidative stress plays a crucial role in maintaining and sustaining cartilage degradation. Current OA management requires a combination of pharmaceutical and non-pharmacological strategies, including intraarticular injections of hyaluronic acid (HA). However, several lines of evidence reported that HA oxidation by reactive oxygen species (ROS) is linked with HA cleavage and fragmentation, resulting in reduced HA viscosity. Resolvin D1 (RvD1) is a lipid mediator that is biosynthesized from omega-3 polyunsaturated fatty acids and is a good candidate with the potential to regulate of panoply of biological processes, including tissue repair, inflammation, oxidative stress, and cell death in OA. Herein, newly designed, and synthesized imidazolium RvD1 analogues were introduced to compare their potential antioxidant properties with commercially available RvD1. Their antioxidant capacities were investigated by several in vitro chemical assays including Oxygen Radical Absorbance Capacity, 2,2-Diphenyl-1-picrylhydrazyl Radical Scavenging, Ferric Ion Reducing Antioxidant Power, Hydroxyl Radical Scavenging, and HA Fragmentation Assay. All results proved that imidazolium RvD1 analogues showed excellent antioxidant performance compared to RvD1 due to their structural modifications. Interestingly, they scavenged the formed reactive oxygen species (ROS) and protected HA from degradation, as verified by agarose gel electrophoresis and gel permission chromatography. A computational study using Gaussian 09 with DFT calculations and B3LYP/6-31 G (d, p) basis set was also employed to study the relationship between the antioxidant properties and chemical structures as well as calculation of the molecular structures, frontier orbital energy, molecular electrostatic potential, and bond length. The results showed that the antioxidant activity of our analogues was higher than that of RvD1. In conclusion, the findings suggest that imidazolium RvD1 analogues can be good candidates as antioxidant molecules for the treatment of oxidative stress-related diseases like OA. Therefore, they can prolong the longevity of HA in the knee and thus may improve the mobility of the articulation.

A proportion of osteoarthritis (OA) patients are unsatisfied with post-operative outcomes following total joint replacement surgery (TJR), with insufficient pain relief or poor functional improvement. Predicting those will have poor outcomes would be beneficial for patients and clinicians. The aim of this study was to determine the relationship between baseline anthropometric data and the concentration of pre-operative serum and peri-operative synovial fluid (SF) cytokines with 7-month post-operative outcomes in a cohort of knee and hip OA patients. 160 OA patients were recruited who were scheduled for TJR. The concentration of 24 cytokines were measured in blood and SF by multiplex assay. EQ5Dindex health status was assessed pre-operatively and at 7-months post-operatively. 13% of patients were identified as non-responders based on EQ5Dindex. Compared to responders, non-responders were of higher BMI, had greater waist and hip circumference and had higher levels of SF leptin but lower levels of SF Resistin (p&lt;0.05). Linear regression analysis found a significant relationship between pre-operative body weight and post-operative response (ΔEQ5Dindex; r=0.222, p=0.049). The combination of body weight with SF amphiregulin and SF IL-6 provided an improved predictive model of post-operative response (r=0.470, p=0.035).

Chondrocytes maintain the normal morphological structure and physiological function of articular cartilage. However, the increased expression of inflammatory mediators and matrix-degrading enzymes in chondrocytes can promote ECM degradation, consequently disrupting the physiological function of articular cartilage and ultimately leading to the onset of osteoarthritis (OA). Usnic acid (UA), an extract derived from plants, possesses multiple bioactive properties including anti-inflammatory and antioxidant effects. Hence, this study aims to explore the molecular mechanisms underlying its protective effects in an in vitro simulated model of OA in rat chondrocytes. In vivo experiments encompassed three groups: Control, Model, and Usnic acid (50 mg/kg), with sample extraction following 12 weeks of administration. Pathological alterations in articular cartilage were evaluated using Safranin O-fast green staining. Immunohistochemistry (ICH) analysis was employed to assess the expression of matrix degradation-related markers. The levels of serum cytokines were quantified via ELISA assays. In this study, primary rat chondrocytes were employed as the experimental subject. After a 24-hour treatment period, culture supernatants, total RNA, total protein, and nuclear protein were extracted from the different chondrocyte groups. ELISA and qPCR methods were used to measure levels of IL-6, TNF-α, and PGE2. WB and qPCR were employed to assess levels of p65, p-p65, IκBα, p-IκBα, Nrf2, HO-1, NQO1 ADAMTS-4, MMP-1, MMP-3, MMP-13, INOS, COX-2, and COL2A1. IF analysis was performed to examine Nrf2, p-p65 and COL2A1. Results: (1) In vivo, intraperitoneal injection of usnic acid (50mg/kg) can alleviate pathological changes in articular cartilage and the levels of inflammatory and oxidative-related matrix in the serum. (2) UA reduced the level of inflammatory cytokines in IL-1β-induced chondrocytes supernatant. (3) UA can produce anti-inflammatory and antioxidant effects and inhibit chondrocytes matrix degradation through the Nrf2 and NF-κB pathways. (3) The mechanism by which UA exerts a protective role in chondrocytes is mediated by Nrf2 Conclusion: UA inhibits the expression of chondrocyte matrix degradation-related components through Nrf2 mediated Nrf2 pathway and NF-κB pathway, promotes the production of protective substances, and ultimately exerts a protective effect on chondrocytes.

Osteoarthritis (OA) poses a growing challenge for the aging population, especially in hip and knee joints, contributing significantly to disability and societal costs. Conventional clinical evaluations, typically performed in controlled settings, face difficulties in capturing the dynamic characteristics of rehabilitation and functioning in real-life scenarios. The study assessed the use of automated unsupervised evaluations in the rehabilitation process for patients after hip and knee replacements. We analyzed data from 1144 individuals who used a digital application after surgery, activity data were collected using the Garmin Vivofit 4. Several parameters such as the Peak 6-Minute Consecutive Cadence (P6MC) and Peak 1-Minute Cadence (P1M) were computed and analyzed on a daily basis. The results indicated that cadence measurements, specifically, can effectively differ among individuals with hip and knee conditions as well as the recovery process. Moreover, these metrics demonstrated a high level of responsiveness in monitoring the progress of recovery, surpassing the effectiveness of simply measuring the total number of steps taken. The study highlighted the capacity of technology-driven, patient-centered rehabilitation to improve accuracy, tailor therapy to individual patients, and increased patient involvement. This research also highlighted the significance of automated, unsupervised assessments in enhancing rehabilitation results for OA patients following hip and knee replacement, as tele-rehabilitation becomes increasingly important.

This study investigated the role of a pattern of microRNA (miRNA) as possible mediators of celecoxib and prescription-grade glucosamine sulfate (GS) effects in human osteoarthritis (OA) chondrocytes. Chondrocytes were treated with celecoxib (1.85 µM) and GS (9 µM), alone or in combination, for 24 hrs, with or without interleukin (IL)-1β (10 ng/mL). Viability was detected by MTT assay, apoptosis and reactive oxygen species (ROS) by cytometry, nitric oxide (NO) by Griess method. Gene levels of miRNA, antioxidant enzymes, nuclear factor erythroid (NRF)2, and B-cell lym-phoma (BCL)2 expressions were analyzed by quantitative real time PCR. Protein expression of NRF2 and BCL2 was also detected at immunofluorescence and western blot. Celecoxib and GS, alone or in combination, significantly increased viability, reduced apoptosis, ROS and NO production and the gene expression of miR-34a, -146a, -181a, -210, in comparison to baseline and to IL-1β. The transfection with miRNA specific inhibitors significantly counteracted the IL-1β activity and potentiated the properties of celecoxib and GS on viability, apoptosis and oxidant system, through NF-κB regulation. The observed effects were enhanced when the drugs were tested in combination. Our data confirmed the synergistic anti-inflammatory and chondroprotective properties of celecoxib and GS, suggesting miRNA as possible mediators.

This study compared condylar volume, length, and articular eminence (AE) characteristics in normal individuals and those with unilateral and bilateral juvenile idiopathic osteoarthritis (JOA). The 116 patients were divided into four groups: control (n=16), affected condyle of unilateral JOA (Aff-Uni) (n=36), non-affected condyle of JOA (NonAff-uni) (n=36), and bilateral JOA (Bi-JOA) (n=28). Volume and length differences in the condyle and AE were analyzed using ANOVA and Bonferroni post hoc tests. The results showed that Bi-JOA had significantly different condylar volume, especially in the condylar head (p&lt;0.01), specifically the middle, anterior, and medial parts (p&lt;0.05). Condylar length also differed among the groups, with differences observed between the control group and the other three groups, as well as between the bilateral group and the other three groups (p&lt;0.01). AE total volume differed between the control group and Aff-Uni. In the detailed comparison, Aff-Uni and NonAff-Uni were smaller than the control group in the posterior, lateral, and medial sections (p&lt;0.05). In conclusion, depending on the involvement of unilateral or bilateral JOA, there were differences in condylar volume and AE compared to the normal control group. Therefore, prognosis should be evaluated by distinguishing between patients with unilateral and bilateral JOA.

Cervi cornu has been extensively used in traditional medicine as an antioxidant and for the treatment of various disorders, including osteoporosis. However, since it is not easy to separate the active ingredient, absorption is not performed well. In this study, we extracted the low molecular weight (843Da) collagen NP-2007 from cervi cornu by enzyme hydrolyzation, and evaluated the therapeutic effect in a monosodium iodoacetate (MIA)-induced rat osteoarthritis model, and identified their molecular mechanisms. NP-2007 was orally administered at 50, 100, and 200 mg/kg for 21 d. Efficacy was evaluated based on serum parameters, inflammatory mediators, and mor-phological and histopathological analyses of knee joints. Production of matrix metalloproteinases, including MMP-2, MMP-3, and MMP-9, in the serum was higher in MIA-treated rats; however, these levels decreased after NP-2007 treatment. Serum levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and prostaglandin E2 were lower in the NP-2007 group than in the MIA group. Furthermore, the administration of NP-2007 resulted in effective preservation of both the synovial membrane and knee cartilage, and significantly decreased the transformation of fibrous tissue. This study indicates that NP-2007 can prevent and alleviate symptoms of osteoarthritis and have applications as a novel arthritis treatment.

The aim of this study was to clarify degradation characteristics in each tissue of the knee complex of a medial meniscectomy (MMx)-induced knee osteoarthritis (KOA) animal model using classical methods and a new comprehensive evaluation method called contrast-enhanced X-ray micro-computed tomography (CEX-μCT), which was developed in the study. Surgical MMx was performed in the right knee joints of five male Wistar rats to induce KOA. At 4 wk post-surgery, the synovitis was evaluated using qPCR. Degradations of the articular cartilage of the tibial plateau were evaluated using classical methods and CEX-μCT. Evaluation of the synovitis demonstrated significantly increased expression levels of inflammation-associated marker genes in MMx-treated knees compared to that in sham-treated knees. Evaluation of the articular cartilage using classical methods showed that MMx fully induced degradation of the cartilage. Evaluation using CEX-μCT showed that local areas of the medial cartilage of the tibial plateau were significantly reduced in MMx-treated knees compared to that in sham-treated knees. On the other hand, total cartilage volumes were significantly increased in MMx-treated knees. Based on the findings of this study, the researchers in KOA research could be helped to select an optimal KOA model to discover new drugs.

The purpose of this study was to investigate the relationship between clinical outcomes and lateral thrust before and after unicompartmental knee arthroplasty (UKA) using inertial measurement sensor units. Eleven knees were evaluated with gait analysis. The varus angular velocity was used to evaluate lateral thrust. The femoro-tibial angle (FTA) and hip-knee-ankle angle (HKA) were used to evaluate lower limb alignment, and Oxford Knee Score (OKS) and Japanese Orthopaedic Association Score (JOA) were used to evaluate clinical outcomes. The mean pre-UKA peak varus velocity was 37.1 ± 9.8°/sec, and that of post-UKA was 28.8 ± 9.1°/sec (p=0.00003). Assuming the definition of lateral thrust is when varus angular velocity is more than 28.1°/sec, 81.8% of patients had lateral thrust preoperatively, but this decreased to 55.6% postoperatively. Both OKS and JOA improved after surgery. In addition, HKA was -7.9° preoperatively and -5.8° postoperatively (p=0.024), and FTA was 181.4° preoperatively and 178.4° postoperatively (p=0.012). There was a positive correlation between postoperative JOA and FTA, indicating that changes in postoperative alignment affected clinical outcomes. This study quantitatively evaluated the disappearance of lateral thrust by UKA, and it found that the stability can be achieved by UKA for unstable knees with lateral thrust.

Autologous micrografting technology (AMT®) involves the use of autologous micrografts to stimulate/enhance the repair of damaged tissue. This study assessed the efficacy and safety of the AMT® procedure in patients with early stages of knee osteoarthritis. Briefly, the AMT® procedure involved extraction of auricular cartilage, disaggregation using the Rigeneracons® SRT in 4.0 mL of saline solution and injection of the disaggregated micrografts into the external femorotibial compartment area of the affected knee. Ten patients (4 men, 6 women; age range: 37─84 years) were included in the study. In all patients, there was a steady improvement in knee instability, pain, swelling, mechanical locking, stair climbing and squatting at 1- and 6-months post-procedure. Improvement in mobility was observed as early as 3 weeks post-procedure in 2 patients. Significant improvements were seen in mean scores of all five subscales of Knee Injury and Osteoarthritis Outcome Score (KOOS [KOOS symptoms, KOOS pain, KOOS ADL, KOOS sport and recreation, and KOOS quality-of-life]) between pre-procedure and 1- and 6-months post-procedure (all p≤0.05). Autologous auricular cartilage micrografts obtained by AMT® procedure (using Rigenera® technology) is an effective and safe protocol in the treatment of early-stage knee osteoarthritis. These encouraging findings need to be validated in a larger patient population.

Background: Low-level (LLLT) and high-intensity laser therapy (HILT) can be beneficial additions to knee osteoarthritis (KOA) rehabilitation exercises; however, it is still being determined which modality is more effective. Aim: To compare the effects of LLLT and HILT as adjuncts to rehabilitation exercise (LL+EX and HL+EX) on clinical outcomes in KOA. Methods: Thirty-four adults with mild to moderate KOA were randomly allocated to either LL+EX (n = 17) or HL+EX (n = 17) groups. All participants underwent their designated laser treatment combined with rehabilitation exercises weekly for twelve consecutive weeks. The Knee Injury and Osteoarthritis Outcome Score (KOOS), Numerical Pain Rating Scale (NPRS), active knee flexion, and Timed Up-and-Go test (TUG) were assessed at baseline and immediately post-intervention. Results: Post-intervention, both groups significantly improved their KOOS, NPRS, active knee flexion, and TUG scores compared to baseline (p &lt; 0.01). The mean difference of change in KOOS, NPRS, and active knee flexion scores for the HL+EX group surpassed the minimal clinically important difference threshold. In contrast, the LL+EX group only demonstrated clinical significance in NPRS scores. Conclusions: Incorporating HILT as an adjunct to usual KOA rehabilitation led to significantly higher improvements in pain, physical function, and knee-related disability compared to LLLT.

Knee osteoarthritis (OA) is the most common joint disease worldwide. Exercise therapy has been identified as a first-line treatment option in patients suffering from knee OA. High-intensity interval training (HIIT) is an innovative exercise modality with potential in improving various disease-related outcomes. The purpose of this review is to explore the impact of HIIT on knee OA symptoms and physical functioning. A comprehensive search of scientific electronic databases was conducted to identify the articles on the effects of HIIT on knee OA. Thirteen studies were included in this review. Nine compared the effects of HIIT with those of low-intensity training, moderate-intensity continuous training, or a control group. Three evaluated the effects of HIIT alone. Eight reported a decrease in knee OA symptoms, and eight reported an increase in physical functioning. HIIT was shown to improve knee OA symptoms and physical functioning, but also aerobic capacity, muscle strength, and quality of life with minimal or no adverse events. However, compared to other exercise modalities, no clear superiority of HIIT was found. HIIT is a promising exercise strategy in patients with knee OA: anyway, the actual quality of evidence remains very low, and more high-quality studies are needed to confirm these promising outcomes.

TGF-ꞵ signaling is a vital regulator for maintaining articular cartilage homeostasis. Runx transcription factors, downstream targets of TGF-ꞵ signaling, have been studied in the context of osteoarthritis (OA). Although Runx partner core binding factor β (Cbfβ) is known to play a pivotal role in chondrocyte and osteoblast differentiation, the role of Cbfβ in maintaining articular cartilage remains obscure. This study investigated Cbfβ as a novel anabolic modulator of TGF-ꞵsignaling and determined its role in articular cartilage homeostasis. Cbfβ significantly decreased in aged mouse articular cartilage and human OA cartilage. Articular chondrocyte-specific Cbfb-deficient mice (Cbfb△ac/△ac) exhibited early cartilage degeneration at 20 weeks old and developed OA at 12 months old. Cbfb△ac/△ac mice showed enhanced OA progression under the surgical-induced mice OA model. Mechanistically, forced expression of Cbfβ rescued Col2α1 and Runx1 expression in Cbfβ-deficient chondrocytes. TGF-ꞵ1-mediated Col2α1 expression failed despite the pSmad3 activation under TGF-ꞵ1 treatment in Cbfβ-deficient chondrocytes. Cbfβ protected Runx1 from proteasomal degradation through Cbfβ/Runx1 complex formation. These results indicate that Cbfβ is a novel anabolic regulator for cartilage homeostasis, suggesting that Cbfβ could protect OA development by maintaining the integrity of the TGF-ꞵ1 signaling pathway in articular cartilage.

Age-related disorders of the musculoskeletal system including sarcopenia, osteoporosis and arthritis represent some of the most common chronic conditions worldwide, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. Collectively, these conditions involve multiple tissues, including skeletal muscle, bone, articular cartilage and the synovium within the joint lining. In this review, we discuss the potential for oligonucleotide therapies to combat the unmet clinical need in musculoskeletal disorders by evaluating the successes of oligonucleotides to modify candidate pathological gene targets and cellular processes in relevant tissues and cells of the musculoskeletal system. Further, we discuss the challenges that remain for the clinical development of oligonucleotides therapies for musculoskeletal disorders and evaluate some of the current approaches to overcome these.

Enhance®Fitness (EF) is an evidence-based exercise program recommended for management of osteoarthritis (OA). However, access to EF is limited in rural areas. Accordingly, we evaluated the feasibility and acceptability of remotely delivered EF in rural, community-dwelling older adults with symptomatic knee OA. A single arm pilot trial of remotely delivered EF classes was conducted. Videoconferencing was used to livestream the instructor-led, 1-hour EF classes 3 days/week for 12 weeks. Outcomes were assessed at baseline and immediately post-intervention. A total of 15 participants were enrolled with a median age of 70 years (interquartile range [IQR]: 67-75) and 14 (93%) were women. Median EF class attendance rate was 91% (IQR: 85-94%). Knee pain, as measured by the Knee injury and Osteoarthritis Outcome Score (KOOS), improved significantly from baseline to 12-week endpoint (mean difference=-11.4 [95% CI:-20.9, -2.0); P=0.02). In addition, participants’ self-reported knee function improved significantly (mean difference in KOOS Function score=-11.8 [95% CI:-18.4, -5.2]; P&lt;0.01) as well as their physical capacity (mean difference in Timed Up and Go test time=1.8 seconds [95% CI: 0.2, 3.4]; P=0.03). All participants (100%) were very satisfied with remotely delivered EF classes and there were no serious adverse events. Findings from this pilot trial indicate that remotely delivered EF is feasible and acceptable in rural older adults with knee OA.

Introduction: Osteoarthritis (OA) and age-related degeneration (ARD) are stimulants for the development of the fabella in the knee joint. This meta-analysis updates previous studies and reviews on the prevalence of the fabella in OA or ARD knee joints. In addition, it provides a quantitative estimation of the fabellar prevalence in knees having OA and ARD. Methodology: Twenty studies comprising of data from 11,056 knee joints were included in the analysis, consisting of 6,819 Knees of OA subjects (including those with age more than 40 years) and 4,237 knees of non-OA subjects (including less than 40years) knees, respectively. 2,434 knees had fabellae present in OA subjects (including more than 40years), and 844 fabellae were present in non-OA subjects (including less than 40years). The Odds and Risk Ratios were calculated. Sensitivity analysis and cumulative analysis were conducted to assess the robustness of the findings. Results: Prevalence of fabella was found to be higher in OA knees, where the Risk Ratio of developing fabella was 2.50 (2.07-3.01). Compared with this, the Risk Ratio for the incidence of fabella in OA with ARD knee was 1.84 (1.66-2.03). The bilateral occurrence of fabella was more common than unilateral. The risk of developing fabella in individuals aged less than forty-year was 63% less than individuals aged more than forty years. Conclusion: OA and ARD would increase the prevalence of fabella by 84%, thus acting as stimulants and risk factors for ossified fabella.

This multi-center, single-blinded, randomized controlled study assessed the efficacy of phased exercise rehabilitation programs in patients who underwent a total knee arthroplasty (TKA) and investigated suitable exercise types, intensities, and frequencies for patients undergoing postoperative rehabilitation. Between January and March 2018, 494 patients who had undergone TKA were treated at two medical centers. Patients were randomized and allocated to the rehabilitation group (n=330) or the control group (n=164; treated with postoperative care). The 100-mm Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), range of motion, and Short-Form 36 (SF-36) scores were assessed and compared between the two groups. The average WOMAC score was 84.40±15.20 in the rehabilitation group and 108.30±3.90 in the control group (p=0.009). The mean VAS score was 2.54±0.16 in the rehabilitation group and 2.87±0.31 in the control group (p=0.024). Furthermore, the range of motion was 125.02±6.20 in the rehabilitation group and 116.40±1.40 in the control group (p=0.017). The mean SF-36 score was 105.40±21.50 in the rehabilitation group and 83.70±5.01 in the control group (p=0.043). This study suggests that the phase rehabilitation program could be more effective at improving pain, knee function, and quality of life than condition postoperative care after TKA.

Platelet and fibrin-rich orthobiologic products, such as autologous platelet concentrates, have been extensively studied and appreciated for their beneficial effects in multiple conditions. PRP and its derivatives, including PRF, have demonstrated encouraging outcomes in clinical and laboratory settings, particularly in the treatment of musculoskeletal disorders such as OA. Although PRP and PRF have distinct characteristics, they share similar properties. The relative abundance of platelets, peripheral blood cells and molecular components in these orthobiologic products stimulate numerous biological pathways. These include inflammatory modulation, augmented neovascularization, and delivery of pro-anabolic stimuli that regulate cell recruitment, proliferation, and differentiation. Furthermore, the fibrinolytic system, which is sometimes overlooked, plays a crucial role in musculoskeletal regenerative medicine by regulating proteolytic activity and promoting the recruitment of inflammatory cells and MSCs in areas of tissue regeneration, such as bone, cartilage, and muscle. PRP acts as a potent signaling agent; however, it diffuses easily, while the fibrin from PRF offers a durable scaffolding effect that promotes cell activity. The combination of fibrin with hyaluronic acid, another well-studied orthobiologic product, has been shown to improve its scaffolding properties, leading to more robust fibrin polymerization. This supports cell survival, attachment, migration, and proliferation. Therefore, the administration of the "power mix" containing HA and autologous PRP + PRF may prove to be a safe and cost-effective approach in regenerative medicine.

Isometric exercises for physiotherapeutic rehabilitation are often prescribed, with little quantification of the load being prescribed. This article aimed to provide a framework and practical examples of how the physiotherapist may take a more quantitative evidence-based approach to isometric assessment, monitoring, and exercise prescription of knee osteoarthritis, by integrating a strain gauge into their practice. Strength measures to monitor were discussed. A series of fourteen studies were reviewed, with the intent of identifying isometric exercises that had been utilized in the rehabilitation of knee osteoarthritis. Of the fourteen studies, the three most identified isometric exercises were seated knee extension, knee flexion, and the supine straight leg raise. The integration of strain gauge technology with these exercises provided the focus of the remainder of the article.

One of the most striking findings in biogerontology in the 2010s was the demonstration that elimination of senescent cells delays many late-life diseases and extends lifespan in mice. This implied that accumulation of senescent cells promotes late-life diseases, particularly through action of senescent cell secretions (the senescence-associated secretory phenotype or SASP). But what exactly is a senescent cell? Subsequent to the initial characterization of cellular senescence it became clear that, prior to aging, this phenomenon is in fact adaptive. It supports tissue remodeling functions in a variety of contexts, including embryogenesis, parturition and acute inflammatory processes that restore normal tissue architecture and function, such as wound healing, tissue repair after infection, and amphibian limb regeneration. In these contexts such cells are normal and healthy, and not in any way senescent in the true sense of the word, as originally meant by Hayflick. Thus, it is misleading to refer to them as “senescent”. Similarly, the common assertion that senescent cells accumulate with age due to stress and DNA damage is no longer safe, particularly given their role in inflammation - a process that becomes persistent in later life. We therefore suggest that it would be useful to update some terminology, to bring it into line with contemporary understanding, and to avoid future confusion. To open a discussion of this issue, we propose replacing the term cellular senescence with remodeling activation, and SASP with RASP (remodeling-associated secretory phenotype).

Modern advances in molecular medicine have led to reframing osteoarthritis as a metabolically active, inflammatory disorder with local and systemic contributing factors. According to the ‘inflammatory theory’ of osteoarthritis, immune response to an initial damage is the key trigger that leads to progressive joint destruction. Several intertwined pathways are known to induce and govern articular inflammation, cartilage matrix degradation, and subchondral bone changes. Effective treatments capable of halting or delaying the progression of osteoarthritis remain elusive. As a result, supplements such as glucosamine and chondroitin sulphate are commonly used despite the lack of scientific consensus. A novel option for adjunctive therapy of osteoarthritis is LithoLexal®, a marine-derived, mineral-rich extract, that exhibited significant efficacy in clinical trials. LithoLexal® has a lattice microstructure containing a combination of bioactive rare minerals. Mechanistic research suggests that this novel treatment possesses various potential disease-modifying properties, such as suppression of nuclear factor kappa-B, interleukin 1β, tumour necrosis factor α, and cyclooxygenase-2. Accordingly, LithoLexal® can be considered a disease-modifying adjunctive therapy (DMAT). LithoLexal® monotherapy in patients with knee osteoarthritis has significantly improved symptoms and walking ability with higher efficacy than glucosamine. Preliminary evidence also suggests that LithoLexal® may allow clinicians to reduce the dose of nonsteroidal anti-inflammatory drugs in osteoarthritic patients by up to 50%. In conclusion, the multi-mineral complex, LithoLexal®, appears to be a promising candidate for DMAT of osteoarthritis, which may narrow the existing gap in clinical practice.

Intra-articular fractures are a major cause of post-traumatic osteoarthritis (PTOA). Despite adequate surgical treatment, the long-term risk for PTOA is high. Previous studies reported that joint injuries initiate an inflammatory cascade characterized by elevation of synovial pro-inflammatory cytokines, which can lead to cartilage degradation and PTOA development. This review summarizes the literature on the post-injury regulation of pro-inflammatory cytokines and the markers of cartilage destruction in patients suffering from intra-articular fractures. METHODS We searched Medline, Embase, and Cochrane databases (1960–February 2020) and included studies that were performed on human participants and included control groups. Two investigators assessed the quality of the included studies using Covidence and the Newcastle-Ottawa Scale. RESULTS Based on the surveyed literature, several synovial pro-inflammatory cytokines, including interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-12p70, interferon-y, and tumor necrosis factor-α, were significantly elevated in patients suffering from intra-articular fractures compared to control. A simultaneous elevation of anti-inflammatory cytokines such as IL-10 and IL-1RA was also observed. In contrast, IL-13, CTX-II, and aggrecan concentrations did not differ significantly between the compared cohorts. CONCLUSIONS Overall, intra-articular fractures are associated with an increase in inflammation-related synovial cytokines. However, more standardized studies which focus on the ratio of pro- and anti-inflammatory cytokines at different time points are needed.

High-frequency near-infrared diode laser provides high peak output, low heat accumulation, and efficient biostimulation. Although these characteristics are considered suitable for osteoarthritis (OA) treatment, the effect of high-frequency near-infrared diode laser in in vitro or in vivo OA models has not yet been reported. Therefore, we aimed to assess the biological effects of high-frequency near-infrared diode laser irradiation on IL-1β-induced chondrocyte inflammation in an in vitro OA model. Normal Human Articular Chondrocyte-Knee (NHAC-Kn) cells were stimulated with human recombinant IL-1β and irradiated with high-frequency near-infrared diode laser (910 nm, 4 or 8 J/cm2). The mRNA and protein expression of relevant inflammation- and cartilage destruction-related proteins was analyzed. IL-1β treatment significantly increased the mRNA levels of IL-1β, IL-6, TNF-α, MMP-1, MMP-3, and MMP-13. High-frequency near-infrared diode laser irradiation significantly reduced the IL-1β-induced expression of IL-1β, IL-6, TNF-α, MMP-1, and MMP-3. Similarly, high-frequency near-infrared diode laser irradiation decreased the IL-1β-induced increase in protein expression and secreted levels of MMP-1 and MMP-3. These results highlight the therapeutic potential of high-frequency near-infrared diode laser in OA.

Osteoarthritis (OA) is a pathology of great impact worldwide which its physiopathology is not completely known and usually diagnosed by imaging techniques performed at advanced stages of the disease. The aim of this study was to evaluate early serum metabolome changes and identify the main metabolites involved in an inflammatory OA animal model. The study was performed with thirty rats, OA in all animals was induced by intra-articular injection of monoiodoacetate into the knee joint. Blood samples were taken from all animals and analyzed by mass spectrometry before OA induction, and 28, 56 and 84 days following induction. Histological study confirmed OA in all samples. The results of this study allow the identification of several changes in the serum metabolome over time, including organic acids, benzenoids, heterocyclic compounds and lipids at T28, organic acids at T56 and lipid classes at T84. We conclude that OA induces serological changes in the metabolome and, more specifically, 18 metabolites which could serve as potential biomarkers. However, it was not possible to establish a relationship between the identified metabolites and the time at which the samples were taken. Therefore, these findings should be confirmed in future OA studies.

Pain in osteoarthritis (OA) results from erosion of joint cartilage, resulting in bone contacting bone without an intervening cushion. The periosteum, including its nociceptive innervation, ends at the border of the cartilage meaning that there is no extrinsic neuronal pathway between the opposing denuded bone surfaces to carry a bone-on-bone pain signal to the brain. The pain signaling pathway must therefore originate in nociceptive sensory endings within the subchondral bone itself. Selective ablation of this intrinsic nerve pathway, using any of a variety of approaches, is expected to permanently eliminate OA pain.

Purpose: Cardiovascular disease (CVD) is a major risk factor for mortality in patients with osteoarthritis, and comorbidities increase postoperative complications after total knee arthroplasty (TKA). Arteriosclerosis plays a major role in hemodynamic dysfunction and CVD; however, arteriosclerosis has not been preoperatively evaluated before TKA using the cardio–ankle vascular index (CAVI). In this study, we evaluated the degree of preoperative arteriosclerosis using the CAVI in patients undergoing TKA, as well as its correlations with several preoperative patient factors. Methods: Arteriosclerosis was evaluated in 209 consecutive patients (251 knees) with osteoarthritis who underwent TKA at our institution between May 2011 and June 2022. The CAVI was measured in the supine position 1 day before TKA, and the correlations between the CAVI and several clinical factors were analyzed. A p value of <0.05 was considered statistically significant. Results: The CAVI was normal in 62 knees (25%), borderline in 71 knees (28%), and abnormal in 118 knees (47%). Univariate analysis revealed a moderate positive correlation between preoperative CAVI and age (r = 0.451, p < 0.001) and a weak negative correlation between preoperative CAVI and body weight (r = −0.306, p < 0.001) and body mass index (BMI) (r = −0.319, p < 0.001). Multivariate analysis showed that age (β = 0.349, p < 0.001) and BMI (β = −0.235, p < 0.001) were significantly correlated with preoperative CAVI. Conclusion: Arteriosclerosis should be carefully managed intraoperatively and postoperatively in patients with osteoarthritis undergoing TKA, particularly in older patients and patients with a low BMI.

DNA methylation is one of the epigenetic mechanisms which have been implicated in cellular differentiation, ageing and disease development. The effect of hypomethylating drug 5-aza-2´deoxycytidine (5-aza dC) on the biosynthetic profile of caudal region chondrocytes from chick sternum was studied in detail. The chondrocytes in culture were treated with varying doses of 5-aza dC for 48h and maintained subsequently without the treatment and harvested at selected time points for analysis of growth and differentiation status. 15µg/ml of 5-aza dC showed optimum Concentration at which there was a significant increase in DNA synthesis and RNA synthesis as per cell basis. There was also a significant increase in total protein synthesis and collagen synthesis as per cell basis at this concentration. This optimal concentration also showed to up regulate the gene expression of Type X collagen and alkaline phosphatase, which are the marker of hypertrophic chondrocyte expression. These results further support the notion that methylation is the major epigenetic factor controlling the differentiation and maturation of chondrocytes.

Musculoskeletal injuries such as equine osteoarthritis, osteoarticular defects, tendonitis/desmitis, and muscular disorders are prevalent among sport horses, with a fair prognosis for returning to exercise or previous performance levels. The field of equine medicine has witnessed rapid and fruitful development, resulting in a diverse range of therapeutic options for musculoskeletal problems. Staying abreast of these advancements can be challenging, prompting the need for a comprehensive review of commonly used and recent treatments. The aim is to compile current therapeutic options for managing these injuries, spanning from simple to complex physiotherapy techniques, conservative treatments including steroidal and non-steroidal anti-inflammatory drugs, hyaluronic acid, and polyacrylamides, to the promising regenerative therapies such as hemoderivatives and stem cell-based therapies. Each therapeutic modality is scrutinized for its benefits, limitations, and potential synergistic actions to facilitate their most effective application for intended healing/regeneration of the injured tissue/organ and subsequent patient recovery. While stem cell-based therapies emerge as particularly promising for equine musculoskeletal injuries, a multidisciplinary approach is underscored throughout the discussion, emphasizing the importance of considering various therapeutic modalities in tandem.

Osteoarthritis (OA) is a prevalent disease and the leading cause of pain, disability, and quality of life deterioration. Our study sought to evaluate the image quality and dose of cone-beam com-puted tomography arthrography (CBCT-A) and compare them to digital radiography (DR) for OA diagnosis. Overall, 32 cases of CBCT-A and DR with OA met inclusion criteria and were prospectively analyzed. The Kellgren and Lawrence classification (KLC) stage, sclerosis, osteo-phytes, erosions, and mean joint width (MJW) were compared between CBCT-A and DR. Image quality was excellent in all CBCT-As, with excellent inter-observer agreement. OA un-der-classification was noticed with DR for MJW (p=0.02), osteophyte detection (<0.0001), and KLC (P<0.0001). The HU values obtained for the CBCT did not correspond to the values for MDCT, with a greater mean deviation obtained with the MDCT HU for MBIR1 than MBIR2. CBCT-A has been found to be more reliable for OA diagnosis than DR as revealed by our results using three-point rating scale for the qualitative image analysis, with higher quality and an ac-ceptable dose. Moreover, the use of this imaging technique permits the preoperative assessment of extremities in OA diagnosis, the upright position and bone microarchitecture analysis being two other advantages of CBCT-A.

Knee Osteoarthritis (KOA), the most common knee degenerative disease, involve a slow destructive process, leading to disability and ultimately total knee replacement. The progression of KOA is related to the loss of rheological properties of the synovial fluid (SF), due to slow immunological, inflammatory and enzymatic processes that cleave the hyaluronic acid (HA) and decrease the concentration of specific proteins. Since no effective treatments have been found to halt the progression of KOA, injection of HA-based viscoelastic gels combined with physiotherapy (PT) is an alternative to symptomatic therapies. In order to evaluate the effect of viscosupplementation and PT on the SF characteristics, the SF aspirated from the KOA was spectrophotometrically and rheological analyzed, comparing the receiving groups of HA Kombihylan® and groups that received Kombihylan® and complex PT. In patients treated with PT, SF extracted 6 weeks after viscosupplementation had a superior elastic moduli (G') and viscous moduli (G") profile behavior, having a homogeneous distribution of proteins and polysaccharides in the SF, stimulating stronger interactions. In the absence of PT the G' and G" profiles are non-uniform, suggesting an unorganized supplemented SF with some clustering phenomena, proteins aggregation and a low level of entanglement between HA and macromolecular components in the SF.

Abstract: Sand-cement bound screed floor layers are at risk for work-related low back pain, lumbosacral radicular syndrome and knee osteoarthritis given their working technique of level-ling screed with their trunk bended and mainly supported by their hands and knees. To reduce the exposure of the physical demands of bending of the trunk and kneeling, a manually moved screed levelling machine was developed for floor layers in the Netherlands. The aim of this pa-per is to estimate the potential health gain of the manually moved screed levelling machine on the risk of low back pain (LBP), lumbosacral radicular syndrome (LRS) and knee osteoarthritis (KOA) compared to the traditional working technique. The potential health gain was assessed using the epidemiological population estimates of the Population Attributable Fraction (PAF) and the Potential Impact Fraction (PIF) combined with work-related risk estimates for these three disorders from systematic reviews. The percentage of workers exceeding these risk esti-mates was based on worksite observations among in total 28 floor layers. For LBP, 16/18 work-ers were at risk using the traditional working technique with PAF=38%, and for the manually moved screed levelling machine this was 6/10 with PIF=13%. For LRS, these data were 16/18 with PAF=55% and 14/18 with PIF=18% and for KOA, 8/10 with PAF=35% and 2/10 with PIF=26%. A manually moved screed levelling machine might have a significant impact on the prevention of LBP, LRS and KOA among floor layers in the Netherlands and a health impact assessment is a feasible approach to assess health gains in an efficient way.

Neuroscience is a vast discipline that deals with the anatomy, biochemistry, molecular biology, physiology and pathophysiology of central and peripheral nerves. Advances made through basic, translational, and clinical research in the field of neuroscience have great potential for long-lasting and beneficial impacts on human health. The emerging field of biological therapy is intersecting with the disciplines of neuroscience and rheumatology, creating new horizons for interdisciplinary and applied research. Biological drugs, growth factors, neuropeptides and monoclonal antibodies are being developed and tested for the treatment of painful arthritic and rheumatic diseases. This concise communication focuses on the solutions provided by the fields of neuroscience and neuroimmunology for real-world clinical problems in the field of rheumatology, focusing on synovial joint pain and the emerging biological treatments that specifically target pathways implicated in osteoarthritis pain in peripheral nerves.

Injuries to the anterior cruciate ligament (ACL) often result in post-traumatic osteoarthritis (PTOA). To better understand the molecular mechanisms behind PTOA development following ACL injury, we profiled ACL injury-induced gene expression changes in knee joints of three mouse strains with varying susceptibility to OA: STR/ort (highly susceptible), C57BL/6 (moderately susceptible) and super-healer MRL/MpJ (not susceptible). Right knee joints of the mice were injured using a non-invasive tibial compression injury model that closely mimics ACL rupture in humans and global gene expression was quantified before and at 1-day, 1-week, and 2-weeks post-injury using RNA-seq. Following injury, STR/ort displayed severe cartilage degeneration while MRL/MpJ had little cartilage damage. Gene expression analysis suggested that prolonged inflammation and elevated catabolic activity in STR/ort injured joints, compared to the other two strains may be responsible for the severe PTOA phenotype observed in this strain. MRL/MpJ had the lowest expression values for several inflammatory cytokines and catabolic enzymes activated in response to ACL injury. Furthermore, we identified several genes highly expressed in MRL/MpJ compared to the other two strains including B4galnt2 and Tpsab1 which may contribute to enhanced healing in the MRL/MpJ. Overall, this study has increased our knowledge of early molecular changes associated with PTOA development.

Casein Kinase ІІ (CK2) is one of the most versatile kinases. Its involvement in almost all cellular pathways makes it the Master Regulator of biochemical processes in a cell. This kinase is essential in regulating inflammation, cell differentiation, and cell cycle regulation. Often simultaneously. Its emerging role in senescence also indicates its function's centrality in cellular metabolism. The strategy to target this kinase to treat musculoskeletal disorders seems effective. These disorders often include a component of inflammation, dysregulated cell differentiation, and aging. This review focuses on CK2 target discovery and the diversity of its substrate interactions. We then transition toward the implication of CK2 in musculoskeletal disorders. Through a summary of current strategies for CK2 targeting with a new approach, we discuss the potential aspects that could be addressed in future drug research.

The bioactivities of collagen-hydrolysates, sulfated glucosamine and a special fatty acid enriched dog-food were tested in a dog patient study as potential therapeutic treatment options in early osteoarthritis. Biophysical, biochemical, cell biological and molecular modeling methods support that these well-defined substances may act as effective nutraceuticals. Importantly, the applied collagen-hydrolysates as well as sulfated glucosamine residues from marine organisms were strongly supported by both an animal model and molecular modeling of intermolecular interactions. Molecular modeling of predicted interaction dynamics were evaluated for the receptor proteins MMP-3 and ADAMTS-5. These proteins play a prominent role in the maintenance of cartilage health as well as innate and adapted immunity. Nutraceuticals data were generated in a veterinary clinical study focusing on mobility and agility. Specifically, key clinical parameters were obtained from blood probes of German shepherd dogs with early osteoarthritis symptoms fed with collagen-hydrolysates or sulfated glucosamines. Collagen-hydrolysate, a chondroprotective food supplement was examined by high resolution NMR experiments. Molecular modeling simulations were used to further characterize the interaction potency of collagen-fragments and glucosamines with protein receptor structures. Potential beneficial effects of collagen-hydrolysates, sulfated glycans (i.e. sulfated glucosamine from crabs and mussels) and lipids, especially, eicosapentaenoic acid (extracted from fish oil) on biochemical and physiological processes are discussed here in the context of human and veterinary medicine.

Abstract: This article provides a brief review of the ontogeny of chondrocytes and the pathophysiology of osteoarthritis (OA), and details how physical exercise improves the health of osteoarthritic joints and enhances the potential of mesenchymal stem cells for successful transplantation therapy. In response to exercise chondrocytes increase their production of glycosaminoglycans, bone morphogenic proteins and antiinflammatory cytokines and decrease their production of proinflammatory cytokines and matrix degrading metalloproteinases. These changes are associated with improvements in cartilage organization and reductions in cartilage degeneration. Studies in humans indicate that exercise increases peripheral blood recruitment of bone marrow-derived mesenchymal stem cells (BM-MSC) and upregulates BM-MSC expression of osteogenic and chondrogenic genes, osteogenic micro-RNAs, and osteogenic growth factors. Rodent experiments are uniform in demonstrating that exercise enhances the osteogenic potential of BM-MSC while diminishing their adipogenic potential, and that exercise done after stem cell implantation may benefit stem cell transplant viability. Physical exercise also exerts a beneficial effect on the skeletal system by decreasing immune cell production of osteoclastogenic cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and interferon (INF)-γ while increasing their production anti-osteoclastogenic cytokines IL-10 and transforming growth factor (TGF)-β. In conclusion, physical exercise done both by stem cell donors and recipients may improve the outcome of mesenchymal stem cell transplantation.

Dysregulation of cartilage homeostasis and the changes in the density and the architecture of the subchondral bone were postulated as a potent mechanically pathological activity contributing to osteoarthritis (OA) pathogenesis. Extracorporeal shockwave therapy (ESWT) is a new, none invasive and effective method in the treatment of animal OA model. In the current study, we demonstrated that shockwave induced the expression of protein-disulfide isomerase-associated 3 (Pdia-3) which is a multifunctional protein hypothesized to be a significant mediator for 1α,25-Dihydroxyvitamin D3 (1α,25(OH)₂D₃) signaling pathway using two-dimensional electrophoresis. Histological analysis and quantitative polymerase chain reaction (qPCR) were verified and observed that the expression of Pdia-3 at 2 weeks was significantly higher than that of any other group at 4 weeks, 8 weeks, and 12 weeks post-shockwave treatment in early OA knee of rat. The other factors of the 1α,25(OH)₂D₃ rapid membrane signaling pathway including extracellular signal-regulated protein kinases 1 (ERK1), osteopontin (OPG), alkaline phosphatase (ALP), and matrix metallopeptidase 13 (MMP13) were measured and significantly increased by qPCR at 2 weeks post-shockwave treatment in early OA knee. Our proteomic data revealed significant Pdia-3 expression in microenvironments of joint tissue that could be actively responded to ESWT, which may potentially regulate biological function of chondrocytes and osteoblasts in the treatment of OA knee.

Preliminary clinical data suggest pain reduction through fasting in different diagnoses. This uncontrolled observational clinical study examined the effects of prolonged modified fasting on pain and functional parameters in hip and knee osteoarthritis. Patients admitted to the inpatient department of Internal Medicine and Nature-based Therapies of the Immanuel Hospital Berlin between February 2018 and March 2020, answered questionnaires at the beginning and end of inpatient treatment, as well as 3, 6 and 12 months after discharge. Additionally, selected blood and anthropometric parameters were routinely assessed during the inpatient stay. Fasting was performed as part of a multimodal integrative treatment program, with daily caloric intake of <600 kcal for 7.7 ± 1.7 days. N=125 consecutive patients were included. Results revealed an amelioration of overall symptomatology (WOMAC Index score: -14.8±13.31; p<0.001; d=0.78), and pain alleviation (NRS Pain: -2.7±1.98, p<0.001, d=1.48). Pain medication was reduced, stopped, or replaced by herbal remedies in 36% of patients. Improvements were also observed in secondary outcome parameters, including increased quality of life (WHO-5: +4.5±4.94, p<0.001, d=0.94), reduced anxiety (HADS-A: -2.1±2.91, p<0001, d=0.55) and depression (HADS-D: -2.3±3.01, p<0.001, d=0.65), decreases in body weight (-3.6 kg ± 1.65, p< 0.001, d=0.21), and blood pressure (systolic: -6.2±15.93, p<0.001, d= 0.43; diastolic: -3.7±10.55, p<0.001, d=0.43). Results suggest that patients with osteoarthritis of the lower extremities may profit from a prolonged fast embedded in a multimodal integrative treatment regarding quality of life, pain, and disease-specific functional parameters. Confirmatory RCTs are warranted to further investigate these hypotheses.

Vitamin D plays an important role in maintaining healthy mineralized skeleton. It is also consid-ered an immunomodulatory agent that regulate the innate and adaptive immune systems. Multi-ple observational studies have demonstrated the association between low level of serum 25-hydroxyvitamin D [25(OH)D] and presence and severity of several rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), spondyloarthropathies and oste-oarthritis (OA). Nevertheless, the specific benefits of vitamin D supplement for treatment and prevention of rheumatic diseases are less accepted as the results from randomized clinical trials are inconsistent, although some conceivable benefits of vitamin D for improvement of disease ac-tivity of RA, SLE and OA have been demonstrated in meta-analyses. It is also possible that some individuals might benefit from vitamin D differently from others since inter-individual difference in responsiveness to vitamin D supplementation has been observed in genomic studies. Although the optimal level of serum 25(OH)D is still debatable, it is advisable it is advisable that patients with rheumatic diseases should maintain serum 25(OH)D level at least 30 ng/mL (75 nmol/L) to prevent osteomalacia, secondary osteoporosis and fracture, and possibly 40 – 60 ng/mL (100 – 150 nmol/L) to achieve maximal benefit from vitamin D for immune health and overall health.

Inflammatory diseases are common pathological processes caused by various acute and chronic factors and some of them are autoimmune diseases. Exosomes are fundamental extracellular vesicles secreted by almost all cells, which contain a series of constituents, i.e. cytoskeletal and cytosolic proteins (actin, tubulin, histones), nucleic acids (mRNA, miRNA, DNA), lipids (diacylglycerophosphates, cholesterol, sphingomyelin, ceramide), and other bioactive components (cytokines, signal transduction proteins, enzymes, antigen presentation and membrane transport/fusion molecules, adhesion molecules). This review would be a synopsis of the actual knowledge on the contribution of exosomes from different cell sources as possible therapeutic agents against inflammation, focusing on several inflammatory diseases, neurological diseases, rheumatoid arthritis and osteoarthritis, intestinal bowel disease, asthma, liver and kidney injuries. Current knowledge indicates that the role of exosomes in therapy of inflammation and in inflammatory diseases could be distinctive. Main limitations to their clinical translation are still production, isolation, and storage. Additionally, there is an urgent need to personalize the treatments in terms of selection of exosomes, their dosages and routes of administration, and a deeper knowledge about their biodistribution, type and incidence of adverse events and long-term effects of exosomes. In conclusion, exosomes can very promising next generation therapeutic option, superior to synthetic nanocarriers and cell therapy, and can represent a new strategy of effective, safe, versatile and selective delivery systems in the future.

Historically, the evaluation and assessment of the clinical response to treatment for canine back pain is subjective and relies on owner and clinician assessment of pain. This study evaluated the use of sequential infrared thermal images as a measure of the response of canine patients with back pain to a prescribed series of photobiomodulation therapy (PBMT) treatments. Qualifying participants had histories of pain and dysfunction associated with spinal osteoarthritis or intervertebral disk disease, or of non-specific uni- or bilateral back pain along the paravertebral epaxial muscles. Each patient was initially thermally imaged prior to PBMT treatment and then received multiple PBMT treatments delivered to the appropriate spinal area on days 1, 2, 3, and 4. Participants were reimaged on day 7. Thermal images provided an objective measure of superficial temperature changes over the area of PBMT treatment of each patient after the PBMT regimen. The temperature correlated with statistically significant changes in Colorado State University Canine Chronic Pain Scale scoring (CPS) and owner assessment using the Canine Brief Pain Inventory (CBPI), which includes a Pain Severity Score (PSS) and Pain Interference Score (PIS). The correlation of objective thermal imaging data with more subjective outcome measures suggests thermal imaging may be a valuable additional tool in monitoring therapy outcome.

Objectives: 1) to demonstrate the anti-inflammatory and anabolic effect of Ozone by determining in serum samples the biochemical levels of IL-6 and IGF-1 in knee osteoarthritis (OA) patients in a real world in Rehabilitation Setting; 2) to evaluate clinical effectiveness by Visual Analog Scale (VAS) and WOMAC scale, and biochemical effect by C-reactive protein (CRP), uric acid and erythrocyte sedimentation rate (ESR). Material and methods: 65 patients with knee OA Kellgren Lawrence (KL) grade 2 or more were analyzed in a retrospective observational study. The study run from January 2018 to September 2021. Inclusion criteria: a) patients 18 years or older; b) with knee OA KL 2º or more; c) biochemical analysis before-and-after treatment; d) pain more than 3 on VAS. Exclusion Criteria: a) previous knee surgery; b) favism; c) pregnancy; d) any other disease that originates lack of collaboration for infiltration. Primary Outcome variables: a) IL-6; b) IGF-1 in diabetes mellitus (DM)/obese and non-DM/non-obese patients; both before-and-after Ozone treatment. Secondary Outcome variables: a) CRP, b) ESR, c) uric acid, d) VAS pain, e) WOMAC pain, function and stiffness. Ozone protocol consisted of 4 sessions (once a week) of an intra-articular infiltration of 20 mL (20µg/mL concentration) of a gas mixture of Oxygen-Ozone 95-5% (produced by Ozone generator Ozonosan-α Plus ®). For biochemical evaluation, SNIBE MAGLUMI ™ IL-6 (CLIA) and SNIBE MAGLUMI ™ IGF-1 (CLIA) kits were used. CRP and uric acid were analyzed by Abbott Alinity c kit; and ESR was evaluated by DIESSE VES MATIC CUBE 30. Results: There is a linear correlation between age and OA severity. IL-6 decreased both in DM and non-DM patients and in all OA KL grades (from 2.7 to 1.59 pg/mL). IGF-1 decreased in total group (OA + DM + obesity) from 112.09 to 107.19 ng/mL. When only knee OA patients were analyzed, Ozone improved IGF-1 levels (from 100.17 to 102.03 ng/mL). Ozone decreased CRP, ESR, uric acid, and improved VAS pain, WOMAC pain, function and stiffness (p<0.05). Conclusions: Ozone is a valid option for the management of knee osteoarthritis in real world Rehabilitation Setting, because of its anti-inflammatory, metabolic and anabolic properties. Ozone downregulates pro-inflammatory IL-6 cytokine. Ozone has a metabolic/hypoglycemic effect on obese/diabetic knee osteoarthritis patients by reducing IGF-1. Ozone has an anabolic effect on non-diabetic/non-obese patients by improving IGF-1. Ozone reduces other biomarkers of inflammation (CRP, ESR and uric acid) and improves, pain, function and quality of life.

Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold certain promise for regenerative medicine. This paper is intended to clarify and facilitate the understanding, development and adoption of regenerative medicine in general and specifically of therapies based on unmodified, autologous adipose-derived regenerative cells (UA-ADRCs). To this end, results of landmark experiments on stem cells and stem cell therapy performed in the labs of the authors are summarized, the most intriguing of which are the following: (i) vascular associated mesenchymal stem cells (MSCs) can be isolated from different organs (adipose tissue, heart, skin, bone marrow and skeletal muscle) and differentiated into ectoderm, mesoderm and endoderm, providing significant support for the hypothesis of the existence of a small, ubiquitously distributed, universal vascular associated stem cell with full pluripotency; (ii) the orientation and differentiation of MSCs are driven by signals of the respective microenvironment; and (iii) these stem cells irrespective of the tissue origin exhibit full pluripotent differentiation potential without any prior genetic modification or the need for culturing. They can be obtained from a small amount of adipose tissue when using the appropriate technology for isolating the cells, and can be harvested from and re-applied to the same patient at the point of care without the need for complicated processing, manipulation, culturing, expensive equipment, or repeat interventions. These findings demonstrate the potential of UA-ADRCs for triggering the development of an entire new generation of medicine for the benefit of patients and of healthcare systems.

Articular cartilage healing and repair is one of the biggest clinical challenges in trauma and orthopaedic medicine, leading to high economic loss due to athletic impairment in sport horses. Multipotent Mesenchymal stem/stromal cells are part of novel therapeutic arsenal aimed at tissue regeneration and restoring organ function. These cells release biomolecules and factors in the culture media, producing the so called conditioned medium, which have a pro-regenerative effect through paracrine mechanisms. Considering this, a therapeutic product combining equine synovial membrane derived Mesenchymal stem/stromal cells and equine umbilical cord stroma-derived Mesenchymal stem/stromal cells conditioned medium was employed. In this work the treatment of two articular defects, in the first phalanx and third metacarpus of the left front limb of a five-year-old horse, is described. Following surgical debridement of the lesions, the treatment comprised two intra-articular administrations of the above-mentioned therapeutic combination, 15 days apart. This was followed by a thorough rehabilitation program. A second-round treatment was performed 6 months later. Diagnostic imaging demonstrated significant improvement of the articular defects. The clinical outcome allowed a full return to the athletic performance demonstrating the safety and potential advantages of this approach when compared with other therapeutic options.

This article focuses on the current state-of-the-art in the area of cellular and molecular biotechnology for over-production of clinically relevant therapeutic growth factors and how the technology can be used for the treatment of osteoarthritis (OA). Transfected and irradiated protein packaging cell lines may be used as “cellular factories” for large-scale production of therapeutic proteins and pro-anabolic growth factors, particularly in the context of cartilage matrix regeneration. We discuss the potential for new innovations in regenerative medicine for degenerative diseases of synovial joints using mammalian protein production platforms, specifically protein packaging cell lines, for over-producing growth factors for cartilage tissue regeneration and give recent examples. Mammalian protein production platforms that incorporate protein packaging cell lines are superior to bacterial expression systems and are likely to have a significant impact on the development of new biological therapies for treating focal cartilage defects and more generally for the treatment of degenerative joint diseases such as OA.

A recent study published in Nature Medicine (Mautner et al., Nat Med 2023 Nov 2. doi: 10.1038/s41591-023-02632-w. Epub ahead of print) reported findings regarding a four-arm parallel, multicenter, single-blind, randomized, controlled clinical trial with 480 patients, aimed at comparing the therapeutic effectiveness of orthobiologic interventions against corticosteroid injections for the treatment of knee osteoarthritis (OA). The study concluded that, one-year post-treatment, all orthobiologic therapies examined were equivalent in effectiveness to each other and to corticosteroid injections. While we commend the scope and methodological rigor of the trial, the publication could be enhanced by a more comprehensive presentation of data to support the conclusions drawn. Particularly, the omission of baseline data for primary outcomes, the missing context to evaluate absolute values, the lack of discussion regarding interindividual variability, and the unexpectedly favorable results for corticosteroids that contrast the established literature, are areas that merit additional examination and insight. Here we aim to highlight these points for consideration, and advocate for the release of supplementary data to facilitate a comprehensive understanding and utilization of this rich dataset.

This review article focuses on the current state-of-the-art in the area of cellular and molecular biotechnology for over-production of clinically relevant therapeutic and anabolic growth factors. We discuss how the currently available tools and emerging technologies can be used for the regenerative treatment of osteoarthritis (OA). Transfected protein packaging cell lines such as GP-293 cells may be used as “cellular factories” for large-scale production of therapeutic proteins and pro-anabolic growth factors, particularly in the context of cartilage regeneration. However, when irradiated with gamma or x-rays, these cells lose their capacity for replication, which actually makes them safe for use as a live cell component of intra-articular injections. This innovation is already here, in the form of TissueGene-C, a new biological drug which consists of normal allogeneic primary chondrocytes combined with transduced GP2-293 cells that overexpress the growth factor transforming growth factor β1 (TGF-β1). TissueGene-C has revolutionized the concept of cell therapy, allowing drug companies to develop live cells as biological drug delivery systems for direct intra-articular injection of growth factors whose half-lives are in the order of minutes. Therefore, in this paper, we discuss the potential for new innovations in regenerative medicine for degenerative diseases of synovial joints using mammalian protein production platforms, specifically protein packaging cell lines, for over-producing growth factors for cartilage tissue regeneration and give recent examples. Mammalian protein production platforms that incorporate protein packaging eukaryotic cell lines are superior to prokaryotic bacterial expression systems and are likely to have a significant impact on the development of new humanized biological growth factor therapies for treating focal cartilage defects and more generally for the treatment of degenerative joint diseases such as OA, especially when injected directly into the joint.