Human bone mesenchymal stem cells-derived exosomes overexpressing microRNA-26a-5p alleviate osteoarthritis via down-regulation of PTGS2.

Osteoarthritis (OA) is a degenerative disease characterized by synovium inflammation and articular cartilage damage. The aberrant expression profile of microRNAs (miRNAs) has been implicated in the cartilage of patients with OA. However, how microRNAs carried by exosomes derived from mesenchymal stem cells (MSCs) associated with OA progression is still unknown. Thus, the current study aimed to elucidate the potential therapeutic role of human bone MSC (hBMSC)-derived exosomal miR-26a-5p in OA progression. Initially, the differentially expressed genes related to OA were identified by microarray analysis which provided data predicting the interaction between miR-26a-5p and PTGS2 in OA. Next, miR-26a-5p and PTGS2 were elevated or silenced to determine their effects on the damage of synovial fibroblasts treated with IL-1β. Exosomes derived from hBMSCs were co-cultured with synovial fibroblasts to explore the effect of hBMSC-derived exosomes carrying miR-26a-5p on synovial fibroblast damage. This effect was further verified by an in vivo experiment. Our results revealed that miR-26a-5p was poorly expressed, while PTGS2 was highly expressed in OA patients and synovial fibroblasts treated with IL-1β. Furthermore, miR-26a-5p was identified to specifically target PTGS2. Additionally, the overexpression of miR-26a-5p exerted an alleviatory effect on the damage of the synovial fibroblasts by repressing PTGS2. Moreover, hBMSC-derived exosomes overexpressing miR-26a-5p retarded damage of synovial fibroblasts in vitro and alleviated OA damage in vivo. Taken together, hBMSC-derived exosomes overexpressing miR-26a-5p serve as a repressor for damage of synovial fibroblasts via PTGS2 in OA, which is of significance for the treatment of OA in rats.