MiR-9-5p promotes M1 cell polarization in osteoarthritis progression by regulating NF-κB and AMPK signaling pathways by targeting SIRT1.

OBJECTIVE:To investigate the roles and regulatory mechanisms of miR-9-5p in the development of osteoarthritis (OA). METHODS:Synovial tissues from mouse OA model and control groups were collected and miR-9-5p expression levels and macrophage markers were measured with qPCR. The function of miR-9-5p in macrophage polarization was analyzed by flow cytometry and qPCR. Various databases were employed to screen the target genes one of which was validated with dual-luciferase analysis. Following the validation, rescue research was applied, and the signaling pathways were analyzed with Western blotting. Finally, the role of miR-9-5p in the progression of OA was validated in the mouse model. RESULTS:MiR-9-5p was highly expressed in the synovial tissues of the OA model and was positively associated with M1 markers. Function analysis demonstrated that miR-9-5p could promote the progression of OA by promoting M1 polarization and inhibiting M2 polarization in vivo and in vitro. The mechanism analysis demonstrated that miR-9-5p could regulate macrophage polarization via NF-κB and AMPK signaling pathways by inhibiting SIRT1 expression. CONCLUSIONS:MiR-9-5p could promote M1 polarization and OA progression by regulating NF-κB and AMPK signaling pathways by inhibiting SIRT1 expression.