Early signs of osteoarthritis in differing rat osteochondral defects.

Preclinical models of osteochondral defects (OCDs) are fundamental test beds to evaluate treatment modalities before clinical translation. To increase the rigor and reproducibility of translational science for a robust "go or no-go," we evaluated disease progression and pain phenotypes within the whole joint for two OCD rat models with same defect size (1.5 x 0.8 mm) placed either in the trochlea or medial condyle of femur. Remarkably, we only found subtle transitory changes to gaits of rats with trochlear defect without any discernible effect to allodynia. At 8-weeks post-surgery, anatomical evaluations of joint showed early signs of osteoarthritis with EPIC-microCT. For the trochlear defect, cartilage attenuation was increased in trochlear, medial, and lateral compartments of the femur. For condylar defect, increased cartilage attenuation was isolated to the medial condyle of the femur. Further, the medial ossicle showed signs of deterioration as indicated with decreased bone mineral density and increased bone surface area to volume ratio. Thus, OCD in a weight-bearing region of the femur gave rise to more advanced osteoarthritis phenotype within a unilateral joint compartment. Subchondral bone remodeling was evident in both models without any indication of closure of the articular cartilage surface. We conclude that rat OCD, placed in the trochlear or condylar region of the femur, leads to differing severity of osteoarthritis progression. As found herein, repair of the defect with fibrous tissue and subchondral bone is insufficient to alleviate onset of osteoarthritis. Future therapies using rat OCD model should address joint osteoarthritis in addition to repair itself.

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 the 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% Confidence Interval (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.