Circ_0008956 contributes to IL-1β-induced osteoarthritis progression via miR-149-5p/NAMPT axis

Abstract

Circular RNAs (circRNAs) have been identified to involve in the pathophysiology of osteoarthritis (OA). Herein, this study aimed to investigate the role and mechanisms underlying circ_0008956 in the process of OA. The expression of circ_0008956 and microRNA (miR)-149-5p and Nicotinamide phosphoribosyl transferase 1 (NAMPT) was detected using quantitative real-time polymerase chain reaction and Western blot assays. Cell viability, apoptosis, cell cycle and extracellular matrix (ECM) degradation were analyzed using cell counting kit-8, flow cytometry, and Western blot assays, respectively. The binding interaction between miR-149-5p and circ_0008956 or NAMPT was confirmed using dual-luciferase reporter assay. Circ_0008956 was highly expressed in OA cartilage tissues and interleukin (IL)-1β mediated chondrocytes. Knockdown of circ_0008956 promoted cell viability, cell cycle, suppressed cell apoptosis, and increased type II collagen and aggracan expression in IL-1β-treated chondrocytes. MiR-149-5p was verified to be a target of circ_0008956, inhibition of miR-149-5p reversed the protective effects of circ_0008956 knockdown on IL-1β-stimulated chondrocytes. NAMPT was a target of miR-149-5p, miR-149-5p attenuated IL-1β-induced growth arrest and ECM degradation in chondrocytes, which was abolished by NAMPT overexpression. Importantly, circ_0008956 served as a sponge for miR-149-5p to up-regulate NAMPT expression in chondrocytes. Circ_0008956 contributed to IL-1β-induced growth arrest and ECM degradation in chondrocytes via miR-149-5p/NAMPT axis, suggesting a new insight into the pathogenesis of OA and a promising therapeutic target for OA treatment.