24R,25-Dihydroxyvitamin D3 Protects against Articular Cartilage Damage following Anterior Cruciate Ligament Transection in Male Rats

Osteoarthritis (OA) in humans is associated with low circulating 25-hydroxyvitamin D3 [25(OH)D(3)]. In vitamin D replete rats, radiolabeled 24R,25-dihydroxyvitamin D3 [24R,25(OH)(2)D(3)] accumulates in articular cartilage following injection of [(3)H]-25(OH)D(3). Previously, we showed that 24R,25(OH)(2)D(3) blocks chondrocyte apoptosis via phospholipase D and p53, suggesting a role for 24R,25(OH)(2)D(3) in maintaining cartilage health. We examined the ability of 24R,25(OH)(2)D(3) to prevent degenerative changes in articular cartilage in an OA-like environment and the potential mechanisms involved. In vitro, rat articular chondrocytes were treated with IL-1β with and without 24R,25(OH)(2)D(3) or 1α,25(OH)(2)D(3). 24R,25(OH)(2)D(3) but not 1α,25(OH)(2)D(3) blocked the effects of IL-1β in a dose-dependent manner, and its effect was partially mediated through the TGF-β1 signaling pathway. In vivo, unilateral anterior cruciate ligament transections were performed in immunocompetent rats followed by intra-articular injections of 24R,25(OH)(2)D(3) or vehicle (t = 0, 7, 14, 21 days). Tissues were harvested on day 28. Joints treated with vehicle had changes typical of OA whereas joints treated with 24R,25(OH)(2)D(3) had less articular cartilage damage and levels of inflammatory mediators. These results indicate that 24R,25(OH)(2)D(3) protects against OA, and suggest that it may be a therapeutic approach for preventing trauma-induced osteoarthritis.