Mesenchymal Stem Cell-Derived Extracellular Vesicles Ameliorate Temporomandibular Joint Osteoarthritis by Suppressing Osteoclast Activity Via let-7a-5p/Integrin β3 Axis.

Temporomandibular joint osteoarthritis (TMJOA) is a common degenerative oral disease and remains one of the most challenging joint disorders to treat clinically. It is characterized by excessive subchondral bone loss at an early stage and cartilage damage at a later stage. In recent years, mesenchymal stem cell (MSC) derived extracellular vesicles (MSC-EVs) have attracted widespread attention for their potential role in modulating OA pathology. However, the application of MSC-EVs in TMJOA remains underexplored, and the mechanisms underlying their therapeutic effects are not fully understood. In this study, we evaluate the therapeutic effects of human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUCMSC-EVs) on TMJOA, with a focus on subchondral bone, and investigate their underlying molecular mechanisms through miRNA sequencing. The results demonstrated that hUCMSC-EVs treatment significantly reduced osteoclast (OC) activity by transferring let-7a-5p, which further suppressed the expression of integrin β3 (ITGβ3) of osteoclasts. In a rat TMJOA model, intra-articular injection of hUCMSC-EVs demonstrated protective effects on both subchondral bone and cartilage, primarily through the suppression of osteoclast activity. Consequently, these results highlight the potential of hUCMSC-EV-based therapies as promising and effective approaches for the treatment of TMJOA.