Abstract: Objective To investigate the role of bone marrow mesenchymal stem cell-derived exosomes (BMSCs-Exo) in the regulation of macrophage phenotypic polarization and cartilage repair in the inflammatory microenvironment. Methods BMSCs-Exo were extracted by differential centrifugation, and the morphology of exosomes was observed by transmission electron microscopy, and the expression of Alix and TSG101 was detected by Western blot. M1 Macrophages and IL-1β-stimulated chondrocytes were treated with different concentrations of BMSCs-Exo (10 μg/mL and 50 μg/mL), and the pro-proliferative capacity of BMSCs-Exo was determined by CCK-8. Western blot and quantitative real-time polymerase chain reaction(qRT-PCR) were used to verify the effects of BMSCs-Exo on the phenotypic polarization of M1 macrophages, inflammation-related expression levels of genes IL-1β, IL-6, and chondrogenesis-related factors COL II, MMP-13, TGF-β1. Results After detection, the BMSCs-Exo were round double-layered vesicles with the expression of Alix and TSG101, promoting macrophage proliferation. Compared with the control group, the expression of M1 polarization marker (iNOS) was decreased and that of M2 polarization marker (Arg-1) was increased in M1 macrophages treated with BMSCs-Exo (P<0.05). The expression of inflammatory genes IL-1β and IL-6 were significantly ameliorated (P<0.05). COL II and TGF-β1 expression was elevated and MMP-13 expression level was down-regulated in inflammatory chondrocytes (P<0.05). Conclusion BMSCs-Exo can induce the polarization of pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages, alleviate the level of inflammatory factor expression, and promote cartilage repair in the inflammatory microenvironment and the remission of osteoarthritis.

Key words: mesenchymal stromal cells, exosomes, macrophages, phenotype, inflammation, bone marrow mesenchymal stem cells, cartilage repair