Journal
BONE
Volume 158, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2022.116372
Keywords
Temporomandibular joint osteoarthritis; SM04690; Cartilage; Wnt16; Fibrocartilage stem cells
Categories
Funding
- National Natural Science Foundation of China (NSFC) [81600888]
- Pearl River S&T Nova Program of Guangzhou [201806010012]
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Studies have shown that SM04690 may promote FCSCs chondrogenesis and repair TMJ cartilage, highlighting its therapeutic potential in TMJOA.
Abnormal Wnt signaling has been shown to be involved in the pathogenesis of temporomandibular joint osteoarthritis (TMJOA). Recent studies demonstrates that SM04690, a small-molecule inhibitor of the Wnt signaling pathway, is able to promote cartilage regeneration in a rat model of knee joint osteoarthritis. However, whether SM04690 has any effect on TMJOA is unknown. Here we first performed partial TMJ discectomy to induce TMJOA in rabbit and rat. Histology, TRAP staining, immunohistochemistry and mu CT analysis showed intra-articular injection of SM04690 protected condylar cartilage from degeneration and attenuated abnormal subchondral bone remodeling of TMJ condylar in both rabbit and rat model TMJOA. We isolated and cultured primary condylar chondrocytes for in vitro studies to investigate molecular mechanisms and downstream effects of SM04690. We found that SM04690 inhibited the canonical Wnt pathway, upregulated the expression of Wnt16 and cartilage anabolic factors including COL2A1, SOX9 and aggrecan, suppressed the expression of cartilage catabolic factor MMP13 and protected chondrocytes from TNF-alpha-induced inflammatory response. Previous studies have identified fibrocartilage stem cells (FCSCs) localized within the TMJ condyle superficial zone niche that regenerate cartilage and repair joint injury. Here we showed that intra-articular injection of SM04690 increased the number of the TMJ condyle superficial zone (SZ) cells in vivo. Further in vitro studies revealed that SM04690 enhanced FCSCs chondrogenesis and formation of cartilaginous-like tissue in pellet cultures. Taken together, our work demonstrates that SM04690 treatment might be able to promote FCSCs chondrogenesis and repair TMJ cartilage, highlighting the therapeutic potential of intra-articular injection of SM04690 in TMJOA.
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