Human Dental Follicle Cell-Derived Small Extracellular Vesicles Attenuate Temporomandibular Joint Cartilage Damage through Inhibiting HIF-2α

Mesenchymal stem cell (MSC)-based therapies for articular cartilage regeneration are effective mostly due to paracrine signals mediated by extracellular vesicles, especially small vesicles (sEV). However, it is unknown whether dental follicle cell-derived sEV (DFC-sEV) affect in temporomandibular joint osteoarthritis (TMJ-OA). In this study, the effects of DFC-sEV on IL-1β-induced mandibular condylar chondrocytes (MCCs) were determined using CCK8 assays, scratch flow cytometry, and Western blot analysis matrix synthesis catabolic proteins. Furthermore, we used an abnormal occlusion-induced rat model intra-articular injection DFC-sEV, pathological changes which observed HE staining, safranin O immunohistochemistry, micro-CT subchondral bone loss. Gene set enrichment (GSEA) was determine related mechanism involved effect DFC-sEV. Immunofluorescence blotting evaluate expression HIF-1α, HIF-2α, MMP13, VEGF MCCs. Then, lentivirus-induced Epas1 overexpression downstream regulators HIF-2α performed. We found that promoted MCCs proliferation migration protected against destruction induced IL-1β. addition, prevented occlusion model. reduced HIF-1α vitro vivo decreased including MMP13 VEGF. Our study indicated attenuated TMJ damage vivo, might be regulation HIF-2α.