Synovial mesenchymal stem cell-derived exosomal miR-485-3p relieves cartilage damage in osteoarthritis by targeting the NRP1-mediated PI3K/Akt pathway

Abstract

Osteoarthritis (OA) is an age-related musculoskeletal disease that results in pain and functional disability. Stem cell therapy has been considered as a promising treatment for OA. In this study, the therapeutic action and potential mechanism of synovial mesenchymal stem cells (SMSCs)-derived exosomes (Exos) in OA cartilage damage were investigated. Cartilage cells were stimulated with IL-1β to establish an in vitro model of OA cartilage damage. Cartilage cell functions were detected by CCK-8, scratch assay, and flow cytometry, respectively. Inflammatory cytokine levels were assessed by ELISA. Target molecule levels were measured by qRT‒PCR and Western blotting. Exos-induced differential expression of miRNAs in cartilage cells were analyzed by microarray analysis. The interaction between miR-485-3p and neuropilin-1 (NRP1) was validated by dual luciferase reporter and RIP assays. We found that treatment with Exos promoted proliferation, migration, and ECM secretion, but restrained apoptosis and inflammation of IL-1β-exposed cartilage cells via up-regulation of miR-485-3p. Additionally, miR-485-3p directly targeted NRP1 to repress NRP1 expression, which subsequently caused inactivation of the PI3K/Akt pathway. The protective effect of Exos on cartilage damage was counteracted by NRP1 overexpression-mediated activation of the PI3K/Akt pathway. In conclusion, Exos delivered miR-485-3p to attenuate IL-1β-induced cartilage degradation by targeting NRP1 and succedent inactivation of the PI3K/Akt pathway. Our findings shed light on the novel protective mechanism of Exos in OA, which suggest that the restoration of miR-485-3p by Exos might be a novel approach for OA treatment.

Keywords

• Osteoarthritis
• Cartilage damage
• Exos
• miR-485-3p
• NRP1