Role of M2 macrophages-derived extracellular vesicles in IL-1β-stimulated chondrocyte proliferation and inflammatory responses.

M2 macrophages-derived extracellular vesicles (M2-EVs) serve as a tool for the delivery of miRNAs and play an anti-inflammatory role in diseases. This study sought to explore the role of (M2-EVs) in the proliferation and inflammatory responses of IL-1β-stimulated chondrocytes. M2 macrophages were induced and characterized, followed by isolation and characterization of M2-EVs. Chondrocytes were treated with 10 ng/mL IL-1β and co-cultured with M2 macrophages transfected with Cy3-labeled miR-370-3p. Cell viability, TNF (tumor necrosis factor)-α, IL(Interleukin)-18, IL-10, miR-370-3p, and sex-determining region Y-related high-mobility-group box transcription factor 11 (SOX11) mRNA were determined via cell counting assay kit, colony formation, ELISA, and qRT-PCR. The binding relationship between miR-370-3p and SOX11 was testified via the dual-luciferase assay. The functional rescue experiment was designed to confirm the role of SOX11. M2-EVs improved chondrocyte viability and colony formation, lowered TNF-α and IL-18, and elevated IL-10. M2-EVs delivered miR-370-3p into chondrocytes to upregulate miR-370-3p. Upregulation of miR-370-3p in M2-EVs enhanced the protective role of M2-EVs in chondrocytes. miR-370-3p inhibited SOX11 transcription. SOX11 overexpression attenuated the protective role of M2-EVs in chondrocytes. Overall, our findings suggested that M2-EVs promote proliferation and suppress inflammatory responses in IL-1β-stimulated chondrocytes via the miR-370-3p/SOX11 axis.