Exosomes derived from SOX9 overexpressing human umbilical cord mesenchymal stem cells ameliorate osteoarthritis by potentially activating autophagy

The exosomes derived from modified mesenchymal stem cells are a promising treatment for osteoarthritis (OA). The aim of this study was to explore the therapeutic effects of SOX9-overexpressing human umbilical cord mesenchymal stem cells (hucMSCs) exosomes on OA and their potential mechanisms. SOX9 was overexpressed in hucMSCs, and the exosomes derived from these modified hucMSCs were isolated (Exos^SOX9). An IL-1β-stimulated OA chondrocytes model and a surgically induced OA rat model were established. These models were subsequently treated with the prepared exosomes. Western blot results indicated that the Exos^SOX9 markedly enhanced the synthesis of cartilage extracellular matrix and inhibited its degradation in vitro. Histological, imaging, immunohistochemical, and chip analysis demonstrated that the Exos^SOX9 markedly alleviated OA progression and decreased serum inflammatory markers in OA rats. Furthermore, the autophagy/Wnt signaling axis served as a potential target pathway for the Exos^SOX9 in both in vivo and in vitro studies. Consequently, the Exos^SOX9 may alleviate OA by simultaneously inhibiting the Wnt pathway and inducing autophagy. The findings indicate that the Exos^SOX9 may represente a promising approach for cell-free therapy in OA.