Chondrogenic primed extracellular vesicles activate miR-455/SOX11/FOXO axis for cartilage regeneration and osteoarthritis treatment

Abstract

Osteoarthritis (OA) is the leading cause of disability worldwide. Considerable progress has been made using stem-cell-derived therapy. Increasing evidence has demonstrated that the therapeutic effects of BMSCs in chondrogenesis could be attributed to the secreted small extracellular vesicles (sEVs). Herein, we investigated the feasibility of applying engineered EVs with chondrogenic priming as a biomimetic tool in chondrogenesis. We demonstrated that EVs derived from TGFβ3-preconditioned BMSCs presented enriched specific miRNAs that could be transferred to native BMSCs to promote chondrogenesis. In addition, We found that EVs derived from TGFβ3-preconditioned BMSCs rich in miR-455 promoted OA alleviation and cartilage regeneration by activating the SOX11/FOXO signaling pathway. Moreover, the designed T3-EV hydrogel showed great potential in cartilage defect treatment. Our findings provide new means to apply biosafe engineered EVs from chondrogenic primed-BMSCs for cartilage repair and OA treatment, expanding the understanding of chondrogenesis and OA development modulated by EV-miRNAs in vivo.