MicroRNA-29b Promotes Subchondral Bone Loss in TMJ Osteoarthritis

Abnormal subchondral bone remodeling plays important roles during osteoarthritis (OA) pathology. Recent studies show that bone marrow mesenchymal stem cells (BMSCs) in osteoarthritic subchondral bones exhibit a prominent pro-osteoclastic effect that contributes to abnormal subchondral bone remodeling; however, the pathologic mechanism remains unclear. In the present study, we used a mouse model with OA-like change in the temporomandibular joint (TMJ) induced by an experimentally unilateral anterior crossbite (UAC) and found that the level of microRNA-29b (miR-29b), but notmiR-29aormiR-29c, was markedly lower in BMSCs from subchondral bones of UAC mice as compared with that from the sham control mice. With an intra-articular aptamer delivery system, BMSC-specific overexpression ofmiR-29bby aptamer-agomiR-29b rescued subchondral bone loss and osteoclast hyperfunction in UAC mice, as demonstrated by a significant increase in bone mineral density, bone volume fraction, trabecular thickness, and the gene expression of osteocalcin andRunx2but decreased trabecular separation, osteoclast number and osteoclast surface/bone surface, and the gene expression of cathepsin K,Trap, Wnt5a, Rankl, andRankas compared with those in the UAC mice treated by aptamer-NC (allP< 0.05). In addition, BMSC-specific inhibition ofmiR-29bby aptamer-antagomiR-29b exacerbated those responses in UAC mice. Notably, although it primarily affectedmiR-29blevels in the subchondral bone (but not in cartilage and synovium), BMSC-specific overexpression ofmiR-29bin UAC mice largely rescued OA-like cartilage degradation, including decreased chondrocyte density, cartilage thickness, and the percentage areas of proteoglycans and type II collagen, while BMSC-specific inhibition ofmiR-29baggravated these characteristics of cartilage degradation in UAC mice. Moreover, we identifiedWnt5a, but notRanklorSdf-1, as the direct target ofmiR-29b. The results of the present study indicate thatmiR-29bis a key regulator of the pro-osteoclastic effects of BMSCs in TMJ-OA subchondral bones and plays important roles in the TMJ-OA progression.