The role and underlying mechanism of dental pulp stem cell-derived exosomal miR-31 in the treatment of osteoarthritis by targeting mTOR to enhance chondrocyte autophagy levels

Abstract

Introduction: Osteoarthritis is the most prevalent progressive musculoskeletal disease. It leads to functional impairment and decreased quality of life. However, the current treatments remain unsatisfactory. Recent studies have revealed that exosomes derived from mesenchymal stem cells offer a promising approach to improve the pathological changes in osteoarthritis, cartilage tissue, and chondrocyte homeostasis. Material and methods: In this in vitro and in vivo study, we studied the effects and mechanisms of dental pulp stem cell-derived exosomes (DPSCexosomes) on osteoarthritis in a mouse model. Results: The study findings showed that a dental pulp stem cell could generate typical characteristic exosomes. The injection of DPSC-exosomes ameliorated destruction of cartilage, promoted matrix synthesis, inhibited cell apoptosis, and decreased the expression of catabolic factors. However, this effect was shown to be almost eliminated when miR-31 antagomir was injected. Conclusions: Furthermore, DPSC-exosomes show an ability to promote autophagy in chondrocytes through mTOR inhibition, in addition to reducing the mTOR luciferase activity. The ability of DPSC-exosomes to partially regulate autophagy was blocked upon inhibition of miR-31. In brief, DPSC-exosomes have a chondroprotective role in a mouse osteoarthritis model. The underlying mechanism is possibly related to miR-31-mediated suppression of the mTOR-autophagy pathway.