Preprint Article Version 1 This version is not peer-reviewed

Comparative Transcriptomics Identifies Novel Genes and Pathways Involved in Post-Traumatic Osteoarthritis Development and Progression

Version 1 : Received: 14 August 2018 / Approved: 14 August 2018 / Online: 14 August 2018 (05:47:38 CEST)

A peer-reviewed article of this Preprint also exists.

Sebastian, A.; Chang, J.C.; Mendez, M.E.; Murugesh, D.K.; Hatsell, S.; Economides, A.N.; Christiansen, B.A.; Loots, G.G. Comparative Transcriptomics Identifies Novel Genes and Pathways Involved in Post-Traumatic Osteoarthritis Development and Progression. Int. J. Mol. Sci. 2018, 19, 2657. Sebastian, A.; Chang, J.C.; Mendez, M.E.; Murugesh, D.K.; Hatsell, S.; Economides, A.N.; Christiansen, B.A.; Loots, G.G. Comparative Transcriptomics Identifies Novel Genes and Pathways Involved in Post-Traumatic Osteoarthritis Development and Progression. Int. J. Mol. Sci. 2018, 19, 2657.

Journal reference: Int. J. Mol. Sci. 2018, 19, 2657
DOI: 10.3390/ijms19092657

Abstract

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.

Subject Areas

osteoarthritis; RNA-seq; STR/ort; C57BL/6; MRL/MpJ; ACL injury; PTOA; regeneration; inflammation; B4galnt2

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.