Entheseal spinal inflammation and new bone formation with progressive ankylosis may occur in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). This study evaluated whether JAK inhibition with tofacitinib modulated the key disease associated cytokines, TNF and IL-17A and whether tofacitinib also modulated bone marrow stromal cell-derived mesenchymal stem cells (MSCs) function including osteogenesis, since post inflammation new bone formation occurs in these conditions. Methods: Conventional entheseal derived αβ CD4+ and CD8+ T-cells were in-vestigated following anti-CD3/CD28 bead stimulation to determine IL-17A and TNF levels in Tofacitinib treated (1000nM) peri-entheseal bone (PEB) and peripheral blood mononuclear cells (PBMC) following ELISA. Bone marrow stromal cell-derived mesenchymal stem cells (MSCs) colony forming unit (CFU-F) and multilineage potential was evaluated using tofacitinib (dosag-es ranging between 100, 500, 1000 and 10000nM). Results: Induced IL-17A and TNF cytokine production from both entheseal CD4+ T-cells and CD8+ T-cells were effectively inhibited by to-facitinib. Tofacitinib treatment did not impact on CFU-F potential or in vitro chondro- and oste-ogenesis. However, tofacitinib stimulation increased MSC adipogenic potential with greater Oil Red O stained area. Conclusion: Inducible IL-17A and TNF production by healthy human enthe-seal CD4+ and CD8+ T-cells was robustly inhibited in vitro by tofacitinib. However, tofacitinib did not impact on MSC osteogenesis but stimulated in vitro MSC adipogenesis, the rele-vance of which needs further evaluation given the adipocytes are associated with new bone formation in SpA.

Several rheumatologic diseases are primarily distinguished by their involvement of bone tissue, where it not only serves as a mere target of the condition but often plays a pivotal role in its pathogenesis. This scenario is particularly prominent in chronic inflammatory arthritis such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). Given the immunological and systemic nature of these diseases, in this review, we report an overview of the pathogenic mechanisms underlying the specific bone involvement, focusing on the complex interactions that occur between bone tissue's own cells and the molecular and cellular actors of the immune system, a recent and fascinating field of interest defined osteoimmunology. Specifically, we have comprehensively elaborated on the distinct pathogenic mechanisms of bone erosion seen in both rheumatoid arthritis and spondyloarthritis, as well as the characteristic process of aberrant bone formation observed in spondyloarthritis. Lastly, chronic inflammatory arthritis lead to systemic bone involvement, resulting in systemic bone loss and consequent osteoporosis, along with increased skeletal fragility.

Axial spondyloarthritis (axSpA) is a chronic rheumatic disease characterised by the presence of inflammatory back pain. In patients with chronic low back pain, the lumbar flexion relaxation phenomenon measured by surface electromiography (sEMG) differs from that in healthy individuals. However, sEMG activity in axSpA patients has not been studied. The purpose of this study was to analyse the flexion relaxation phenomenon in axSpA patients. A study evaluating 39 axSpA patients and 35 healthy controls was conducted. sEMG activity at the erector spinae muscles was measured during lumbar full flexion movements. sEMG activity was compared between axSpA patients and the controls, as well as between active (BASDAI≥4) and non-active (BASDAI<4) patients. The reliability (using intraclass correlation coefficients (ICC)), criterion validity and discriminant validity using the area Under the curve (AUC) for the inverse flexion/relaxation ratio (1/FRR) were evaluated. Significant differences (p<0.05) were observed between axSpA patients and the control group in lumbar electric activity, especially during flexion, relaxation and extension and in FRR and 1/FRR (0.66±0.39 vs. 0.25±0.19, respectively). In addition, significant differences were found between active and non-active but also between non-active and healthy subjects. The sEMG showed good reliability (ICC>0.8 for 1/FRR) and criterion validity. ROC analysis showed good discriminant validity for axSpA patients (AUC=0.835) vs. the control group using 1/FRR. An abnormal flexion/relaxation phenomenon exists in axSpA patients compared with controls. sEMG could be an additional objective tool in the evaluation of patient function and disease activity status.

Spondyloarthritis comprises of a group of inflammatory diseases of the joints and spine with various clinical manifestations. The group includes ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated spondyloarthritis. The exact etiology and pathogenesis of spondyloarthritis are still unknown, but five hypotheses explaining the pathogenesis exist. These hypotheses suggest that spondyloarthritis is caused by arthritogenic peptides, an unfolded protein response, HLA-B27 homodimer formation, malfunctioning endoplasmic reticulum aminopeptidases, and, last but not least, gut inflammation and dysbiosis. Here we discuss the five hypotheses and the evidence supporting each. In all of these hypotheses, HLA-B27 plays a central role. It is likely that a combination of these hypotheses, with HLA-B27 taking center stage, will eventually explain the development of spondyloarthritis in predisposed individuals.