Exosomes Derived from Quercetin-Treated Bone Marrow Derived Mesenchymal Stem Cells Inhibit the Progression of Osteoarthritis Through Delivering miR-124-3p to Chondrocytes

Abstract

Osteoarthritis (OA) is a chronic disease characterized by the progressive loss of cartilage and failure of the diarrheal joint. Quercetin has been reported to attenuate the development of OA. Bone marrow derived mesenchymal stem cell (BMSC)-derived exosomes are involved in OA progression. However, the role of BMSC-derived exosomes in quercetin-mediated progression of OA remains unclear. Western blotting and RT-qPCR were used to assess protein and mRNA levels, respectively. CCK8 assay was performed to assess cell viability, and cell apoptosis was assessed using flow cytometry. A dual-luciferase assay was performed to assess the relationship between miR-124-3p and TRAF6 expression. Furthermore, in vivo experiments were performed to test the function of exosomes derived from Quercetin-treated BMSCs in OA patients. IL-1β significantly inhibited the viability of chondrocytes, whereas the conditioned medium of Quercetin-treated BMSCs (BMSCs^QUE-CM) reversed this phenomenon through exosomes. IL-1β notably upregulated MMP13 and ADAMT5 and reduced the expression of COL2A1 in chondrocytes, which were rescued by BMSCs^QUE-CM. The effects of BMSCs^QUE-CM on these three proteins were reversed in the absence of exosomes. Exosomes can be transferred from BMSCs to chondrocytes, and exosomes derived from Quercetin-treated BMSCs (BMSCs^Que-Exo) can reverse the apoptotic effects of IL-1β on chondrocytes. The level of miR-124-3p in BMSCs was significantly upregulated by quercetin, and miR-124-3p was enriched in BMSCs^Que-Exo. TRAF6 was identified as a direct target of miR-124-3p, and BMSCs^Que-Exo abolished the IL-1β-induced activation of MAPK/p38 and NF-κB signaling. Furthermore, BMSCs^Que-Exo significantly attenuated OA progression in vivo. Exosomes derived from Quercetin-treated BMSCs inhibited OA progression through the upregulation of miR-124-3p.

Keywords: BMSC; exosome; miR-124-3p; quercetin.