Background/Purpose: While osteoarthritis (OA) in humans is characterized by cartilage degradation, osteophyte formation and joint remodeling, inflammation and synovitis are now recognized to contribute to joint pathology. Two experimental models of OA, destabilization of the medial meniscus (DMM) and section of the anterior cruciate ligament (ACL), are commonly used in the study of OA. While these models mimic many of the changes observed in human OA, the role of synovitis and inflammation remains unclear. To address this, inflammation in DMM and ACL models was evaluated.

Methods: All murine procedures were Home Office (UK) approved. OA was induced in 10 week old C57BL/6 male mice by DMM or ACL. SHAM operated and naïve animals were used as controls. Freund’s complete adjuvant (FCA) monoarthritis model was used as a positive control of inflammatory joint disease. Knee joint diameter was assessed prior to induction of arthritis and then every three days thereafter. IVIS technology was used to assess myeloperoxidase activity. After 4 weeks synovium was harvested and used for explant culture. Supernatants were collected after 4 hours and analyzed by Luminex for the presence of inflammatory mediators. In parallel experiments, joints were collected for histological analysis of CD3+ and F4/80+ cells. Data were expressed as mean ± SEM with p<0.05 taken as the criterion of significance, tested using 1 or 2 way ANOVA.

Results: There was no significant change in the knee joint diameter between naïve, SHAM, DMM and ACL at 4 week time point. However, knee joint diameter significantly increased in FCA compared to all other groups (figure 1A) and it was the only model demonstrating elevated myeloperoxidase activity. Also, elevated levels of IL-1β, IFNγ, RANTES and IL-10 were only detected in FCA explant cultures. While histological analysis of the joints demonstrated an absence of CD3+ T cells in both DMM and ACL models, F4/80+ cells were observed within/adjacent to the anterior cruciate ligament in ACL and at the medial collateral ligament in DMM. Importantly, MIP-1β/CCL4 was significantly increased in FCA and OA surgical models compared to naïve (figure 1B). IL-33 was elevated in FCA and ACL models but did not attain significance for DMM (figure 1C).

Conclusion: This study demonstrates that the OA inflammatory milieu within the DMM and ACL synovium differs substantially from the FCA model. Nevertheless, the presence of F4/80+ cells and high levels of MIP-1β/CCL4 within the synovium as well as elevated IL-33 suggests an ongoing low-grade inflammatory process in these OA models.

Acknowledgements: This research was supported by an Arthritis Research UK programme grant (20199). A. Ortiz was supported by University of the West of Scotland PhD studentship. L. Dunning was supported by the Carnegie Trust for the Universities of Scotland.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/differential-inflammatory-profile-in-experimental-models-of-arthritis/