Modeling Osteoarthritis: MiR-16-5p Attenuates IL-1β Induced Chondrocyte Dysfunction by Targeting MAP2K1 through the MAPK Pathway

Objective: Osteoarthritis (OA) is a chronic joint disease characterized by cartilage degeneration, significantly reducing the quality of life. Previous report has confirmed that MAP2K1 acts as a potential therapeutic target in OA. Nevertheless, its specific function and related molecular mechanism in OA remain uncharacterized. Our report revealed the biological significance of MAP2K1 and elucidated its regulatory mechanism in OA.

Methods: Interleukin (IL)-1β was utilized to stimulate human chondrocyte cell line CHON-001 for establishing the in vitro models of OA. Cell apoptosis and viability were determined by flow cytometry analysis and CCK-8 assay. Protein levels and gene expression were quantified by western blotting and RT-qPCR. Binding relation between miR-16-5p and MAP2K1 (mitogen-activated protein kinase kinase 1) was confirmed by luciferase reporter assay.

Results: IL-1β treatment triggered CHON-001 cell injury by repressing cell viability and facilitating cell apoptosis. Moreover, IL-1β stimulation upregulated MAP2K1 level in CHON-001 cells. MAP2K1 depletion attenuated IL-1β-elicited CHON-001 cell injury. Mechanistically, miR-16-5p targeted MAP2K1 in CHON-001 cells. In rescue assays, MAP2K1 upregulation counteracted the suppressive impact of miR-16-5p enhancement on IL-1β-triggered CHON-001 cell dysfunction. In addition, upregulated miR-16-5p suppressed IL-1β-elicited activation of MAPK pathway in CHON-001 cells.

Conclusions: MiR-16-5p mitigates IL-1β-induced damage to chondrocyte CHON-001 by targeting MAP2K1 and inactivating the MAPK signaling.