BMSCs-derived Mitochondria Improve Osteoarthritis by Ameliorating Mitochondrial Dysfunction and Promoting Mitochondrial Biogenesis in Chondrocytes

Abstract

Bone marrow mesenchymal stem cells (BMSCs)-derived exosomes and microvesicles can effectively improve knee osteoarthritis. We found that microvesicles performed a superior effect on improving mitochondrial function in chondrocytes than exosomes, which may be related to the ability of microvesicles carrying active mitochondria to replace damaged ones in chondrocytes. This study investigated the therapeutic effect of direct mitochondrial transplantation (MT) on knee osteoarthritis. IL-1β stimulated the osteoarthritis phenotype of rat chondrocytes, and the effect of BMSCs-derived mitochondria transplantation was observed in vitro. Knee osteoarthritis rat model was established by collagenase induction to observe the effect of intra-articular injection of mitochondria. Results showed that the mitochondria of BMSCs could be ingested by rat chondrocytes via co-incubation in vitro, and significantly improved osteoarthritis phenotype and mitochondrial function, and inhibited chondrocytes apoptosis. In vivo, BMSCs-derived mitochondria could be ingested by cartilage via intra-articular injection, ameliorated pathological cartilage injury, suppressed inflammation, inhibited chondrocytes apoptosis, and improved osteoarthritis phenotype. In addition, MT promoted mitochondrial biogenesis in chondrocytes by activating PGC-1α signaling. All above results suggest that BMSCs-derived mitochondria transplantation ameliorates knee osteoarthritis by improving chondrocytes mitochondrial dysfunction and promoting mitochondrial biogenesis.