Affiliation:
1. Yunnan Key Laboratory of Stomatology, School of Stomatology, Kunming Medical University, Kunming, China
2. Department of Orthodontics, Kunming Medical University Affiliated Stomatological Hospital, Kunming, China
3. Kunming Medical University, Kunming, China
Abstract
Mesenchymal stem cell (MSC)-based therapies for articular cartilage regeneration are effective mostly due to paracrine signals mediated by extracellular vesicles, especially small extracellular vesicles (sEV). However, it is unknown whether dental follicle cell-derived sEV (DFC-sEV) affect cartilage regeneration 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 assays, flow cytometry, and Western blot analysis of matrix synthesis and catabolic proteins. Furthermore, we used an abnormal occlusion-induced rat model and intra-articular injection of DFC-sEV, the pathological changes of which were observed by HE staining, safranin O staining, immunohistochemistry, and micro-CT analysis of subchondral bone loss. Gene set enrichment analysis (GSEA) was used to determine the related mechanism involved in the effect of DFC-sEV. Immunofluorescence analysis and Western blotting were used to evaluate the expression of HIF-1α, HIF-2α, MMP13, and VEGF in MCCs. Then, lentivirus-induced Epas1 overexpression and Western blot analysis of the downstream regulators of HIF-2α were performed. We found that DFC-sEV promoted MCCs proliferation and migration and protected against cartilage matrix destruction induced by IL-1β. In addition, DFC-sEV prevented cartilage destruction in an abnormal occlusion rat model. Furthermore, we found that DFC-sEV reduced the expression of HIF-1α and HIF-2α in vitro and in vivo and decreased the downstream regulators of HIF-2α, including MMP13 and VEGF. Our study indicated that DFC-sEV attenuated TMJ cartilage damage in vitro and in vivo, which might be involved in the regulation of HIF-2α.
Funder
National Natural Science Foundation of China
Subject
Biomedical Engineering,Biomaterials,Medicine (miscellaneous)