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

IntroductionOsteoarthritis is the most prevalent musculoskeletal progressive disease that leads to functional impairment and decreased quality of life. However, the current treatments remain unsatisfactory. Recent studies reveal that exosomes derived from mesenchymal stem cells offer a promising approach to improve the pathological changes of osteoarthritis, cartilage tissue, and chondrocyte homeostasis.Material and methodsA randomized, controlled animal experiment was conducted on nine-week-old male C57BL/6 mice that were obtained from Charles River Laboratories. In this in vitro and in vivo study, we studied the role and mechanisms of dental pulp stem cell-derived exosomes (DPSCs-exosomes) on osteoarthritis in the mouse model.ResultsThe study findings showed that a dental pulp stem cell could generate typical-characteristic exosomes. The injection of DPSCs-exosomes ameliorated destruction of cartilage, promoted matrix synthesis, inhibited cell apoptosis, and decreased the catabolic factors expression. However, this effect was shown to be almost eliminated when miR-31 antagomir was injected.ConclusionsFurthermore, DPSCs-exosomes show an ability to promote autophagy in chondrocytes through mTOR inhibition, in addition to reducing the mTOR luciferase activity. The ability of DPSCs-exosomes to partially regulate autophagy was blocked upon inhibition of miR-31. In brief, DPSCs-exosomes have a chondroprotective role in the mice osteoarthritis model. The underlying mechanism is possibly related to miR-31-mediated suppression of the mTOR-autophagy pathway.