Analysis for Osteoarthritis of the Ankle Joint in a Mouse Model of Chronic Ankle Instability

Abstract Background Ankle sprains are the most common orthopedic pathology experienced during sports and physical activity and often result in chronic ankle instability (CAI). The purpose of this study was to assess osteoarthritic changes in the ankle joint in a surgical CAI mouse model. Method The experiments were performed using 14-week-old ICR male mice (n = 19). Mice were randomly placed into the SH group (sham; control, n = 5), ATFL group (resected anterior talofibular ligament; mild ankle sprain, n = 7), or ATFL + CFL group (resected anterior talofibular ligament / calcaneofibular ligament; severe, n = 7) and housed individually. Behavioral analysis using the frequency of standing on the hind leg was performed. To evaluate the clinical severity of arthritis, bodyweight, paw thickness, and ankle thickness were assessed immediately before sacrifice. Immunohistochemical staining and micro-computed tomography were performed to analyze the arthritic changes of the ankle joint. Serological analysis of inflammatory cytokines and C-terminal telopeptide of type I bone resorption markers was performed using enzyme-linked immunosorbent assay (ELISA). Results Compared with the control group, the ATFL + CFL group significantly aggravated the clinical severity of arthritis. In the ATFL and ATFL + CFL groups, the number of mice standing on the hind leg was significantly decreased. ELISA confirmed that the inflammatory cytokines were significantly increased in the ATFL + CFL group. C-terminal telopeptide of type I levels were increased in the ATFL + CFL group but the difference was not statistically significant. Conclusions This study demonstrated that the surgical induction of chronic ankle instability (ATFL + CFL) in a mouse model results in the development of osteoarthritis of an ankle joint.