MicroRNA-29b Promotes Subchondral Bone Loss in TMJ Osteoarthritis

Abstract

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 not miR-29a or miR-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 of miR-29b by 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 and Runx2 but decreased trabecular separation, osteoclast number and osteoclast surface/bone surface, and the gene expression of cathepsin K, Trap, Wnt5a, Rankl, and Rank as compared with those in the UAC mice treated by aptamer-NC (all P < 0.05). In addition, BMSC-specific inhibition of miR-29b by aptamer-antagomiR-29b exacerbated those responses in UAC mice. Notably, although it primarily affected miR-29b levels in the subchondral bone (but not in cartilage and synovium), BMSC-specific overexpression of miR-29b in 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 of miR-29b aggravated these characteristics of cartilage degradation in UAC mice. Moreover, we identified Wnt5a, but not Rankl or Sdf-1, as the direct target of miR-29b. The results of the present study indicate that miR-29b is a key regulator of the pro-osteoclastic effects of BMSCs in TMJ-OA subchondral bones and plays important roles in the TMJ-OA progression.

Aberrant Fluid Shear Stress Contributes to Articular Cartilage Pathogenesis via Epigenetic Regulation of ZBTB20 by H3K4me3

“…In vivo, we adopted UAC model which could produce abnormalities in bite force direction and distribution to mimic the natural pathogenesis process of aberrant occlusion-induced TMJOA in human beings as previously described. 21 , 27 , 28 Micro-CT analysis results suggested a decrease of BMD, BV/TV, Tb.Th, and Tb.N in UAC group while Tb.Sp was increased when compared to sham controls ( Figure 7A ). mRNA expression level of Col2 and Sox9 was downregulated, Cox-2 and Mmp13 was upregulated in UAC group ( Figure 7B ).…”

Comparison and applicability of three induction methods of temporomandibular joint osteoarthritis in murine models

“…Studies have reported that bone marrow mesenchymal stem cells (BMSCs) in osteoarthritic subchondral bones show a prominent pro‐osteoclastic activity, resulting in the abnormal subchondral bone remodelling 38,39 . Sun 40 demonstrated that there was subchondral bone loss and osteoclast hyperfunction in UAC mice, and it could be rescued by BMSC‐specific overexpression of miR‐29b by aptamer‐agomiR‐29b. Additionally, it has been found that overextension of the mandible induced subchondral bone loss in the early stages, and osteoblasts and osteoclasts of the condyle subchondral bone were activated 41 .…”

Electroactive Biomaterials for Facilitating Bone Defect Repair under Pathological Conditions

“…It predominantly involves the destruction of articular cartilage, although there is also a gradual degeneration and loss of the subchondral bone that lies adjacent to cartilage tissue and provides it with nutritional and mechanical support. [ 67 , 68 ] The role of subchondral bone in OA pathology has gained more attention in recent years, with the gradual realization that the pathophysiology of OA involves intimate cross talk between subchondral bone and articular cartilage. [ 69 , 70 ] Indeed, a functional complex known as the bone–cartilage unit is formed by subchondral bone and cartilage, which is implicated in OA pathophysiology at the mechanical and biochemical levels.…”