Mild Exercise Expedites Joint Clearance and Slows Joint Degradation in a Joint Instability Model of Osteoarthritis in Male Rats

Objective Exercise remains a hallmark treatment for post-traumatic osteoarthritis (PTOA) and may maintain joint homeostasis in part by clearing inflammatory cytokines, cells, and particles. It remains largely unknown whether exercise-induced joint clearance can provide therapeutic relief of PTOA. In this study, we hypothesized that exercise could slow progression of preclinical PTOA in part by enhancing knee joint clearance. Design Surgical medial meniscal transection was used to induce PTOA in 3-month-old male Lewis rats. A sham surgery was used as a control. Mild treadmill walking was introduced 3 weeks post-surgery and maintained to 6 weeks post-surgery. Gait and isometric muscle torque were measured at the study endpoint. Near-infrared imaging tracked how exercise altered lymphatic and venous knee joint clearance during discrete time points of PTOA progression. Results Exercise mitigated joint degradation associated with PTOA by preserving glycosaminoglycan content and reducing osteophyte volume (effect size (95% CI); 1.74 (0.71-2.26). PTOA increased hind step widths (0.57 (0.18-0.95) cm), but exercise corrected this gait dysfunction (0.54 (0.16-0.93) cm), potentially indicating pain relief. Venous, but not lymphatic, clearance was quicker 1-, 3-, and 6-weeks post-surgery compared to baseline. The mild treadmill walking protocol expedited lymphatic clearance rate in moderate PTOA (3.39 (0.20-6.59) hrs), suggesting exercise may play a critical role in restoring joint homeostasis. Conclusions We conclude that mild exercise has the potential to slow disease progression in part by expediting joint clearance in moderate PTOA.