Exosome-Encapsulated microRNA-127-3p Released from Bone Marrow-Derived Mesenchymal Stem Cells Alleviates Osteoarthritis Through Regulating CDH11-Mediated Wnt/β-Catenin Pathway

OBJECTIVE: Exosome-encapsulated microRNAs (miRNAs) are being considered as either diagnostic or predictive markers in different types of diseases. Here, we discussed the effects of exosome-encapsulated miR-127-3p from bone marrow-derived mesenchymal stem cells (BM-MSCs) on osteoarthritis (OA). METHODS: BM-MSCs and primary chondrocytes were isolated from Sprague Dawley rats. IL-1β was utilized to treat chondrocytes to mimic an OA in vitro model, and exosomes extracted from BM-MSCs were utilized to treat chondrocytes so as to verify their protective effects on OA. Through online website prediction and experiments confirmation, we found the most significantly enriched miRNA in exosomes and elucidated the effect of this miRNA on the therapeutic effect of exosomes by interfering with its expression. Also, the genes targeted by the miRNA and the involved pathway were also found through bioinformatics analysis and experimental research, thereby probing into the protective mechanism of exosomes on chondrocytes. RESULTS: Exosomes derived from BM-MSCs restricted the IL-1β-induced chondrocytes damage. miR-127-3p was found to be enriched in exosomes, and the protective effect of exosomes was reversed by miR-127-3p inhibition. miR-127-3p targeted CDH11, and overexpressed CDH11 in chondrocytes weakened the therapeutic effect of exosomes. IL-1β treatment resulted in the activation of the Wnt/β-catenin pathway in chondrocytes. Exosomes treatment could inhibit the activation of this pathway, and overexpressed CDH11 reversed the inhibitory effect of exosomes on this pathway. CONCLUSION: This study suggests that exosomal miR-127-3p derived from BM-MSCs inhibits CDH11 in chondrocytes, thereby blocking the Wnt/β-catenin pathway activation and relieving chondrocyte damage in OA.