Strontium ranelate reduces cartilage degeneration and subchondral bone remodeling in rat osteoarthritis model

Aim: To investigate whether strontium ranelate (SR), a new antiosteoporotic agent, could attenuate cartilage degeneration and subchondral bone remodeling in osteoarthritis (OA). Methods: Medial meniscal tear (MMT) operation was performed in adult SD rats to induce OA. SR (625 or 1800 mg.kg(-1).d(-1)) was administered via gavage for 3 or 6 weeks. After the animals were sacrificed, articular cartilage degeneration was evaluated using toluidine blue 0 staining, SOX9 immunohistochemistry and TUNEL assay. The changes in microarchitecture indices and tissue mineral density (TMD), chemical composition (mineral-to-collagen ratio), and intrinsic mechanical properties of the subchondral bones were measured using micro-CT scanning, confocal Raman microspectroscopy and nanoindentation testing, respectively. Results: The high-dose SR significantly attenuated cartilage matrix and chondrocyte loss at 6 weeks, and decreased chondrocyte apoptosis, improved the expression of SOX9, a critical transcription factor responsible for the expression of anabolic genes type II collagen and aggrecan, at both 3 and 6 weeks. Meanwhile, the high-dose SR also significantly attenuated the subchondral bone remodeling at both 3 and 6 weeks, as shown by the improved microarchitecture indices, TMD, mineral-to-collagen ratio and intrinsic mechanical properties. In contrast, the low-dose SR did not significantly change all the detection indices of cartilage and bone at both 3 and 6 weeks. Conclusion: The high-dose SR treatment can reduce articular cartilage degeneration and subchondral bone remodeling in the rat MMT model of OA.