Journal
JOURNAL OF DENTAL RESEARCH
Volume 99, Issue 13, Pages 1469-1477Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0022034520937617
Keywords
Wnt-5a; bone marrow mesenchymal stem cells (BMSCs); RNA aptamer; agomirs; antagomirs; osteogenesis
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Funding
- National Natural Science Foundation of China [81870787, 81671012, 81800939]
- Scientific Young Alma of Shannxi Province [2017KJXX-10]
- Youth Innovation Team of Shaanxi Province, Innovation and Development Foundation of Sixth Medical Center of PLA General Hospital [CXPY201819]
- Special Fund of Logistics Health Care of PLA [14BJZ38]
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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.
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