MIR-27 inhibits the NF-κB signaling pathway by targetingleptin in osteoarthritic chondrocytes

Abstract

Osteoarthritis (OA) is a chronic degenerative joint disease. An increasing number of studies point to the role of microRNAs (miRNAs or miRs) in the pathogenesis of OA. An earlier study suggested that miR-27b was associated with OA; however, the precise mechanisms regarding the involvement of the miR-27 in the progression of OA remain unclear. In the present study, we first analyzed the effects of miR-27 on OA. In vitro, the degree of miR-27 expression was decreased in chondrocytes obtained from patients with OA. Transfection with miR-27 mimic increased the viability of CH8 cells and induced the expression of type-II collagen, type-X collagen, glycosaminoglycan (GAG) and aggrecan (ACAN). The results of luciferase activity assay revealed that miR-27 directly targeted the 3'-untranslated region (3'-UTR) of leptin. The results of western blot analysis and ELISA indicated that the concentration of leptin was decreased after the CH8 cells were transfected with miR-27 mimic. In vivo, a rat model of OA was established by anterior cruciate ligament transection (ACLT). When the rats with OA were injected with miR-27 lentiviral overexpression vector, the results of ELISA revealed that the levels of interleukin (IL)-6 and IL-8 were decreased. The results of western blot analysis revealed that matrix metalloproteinase (MMP)-9 and MMP-13 expression levels were decreased, and the nuclear factor-κB (NF-κB) pathway was inhibited. On the whole, our results suggest that the upregulation of miR-27 inhibits the pathogenesis of OA by targeting leptin and inhibiting the NF-κB signaling pathway. Thus, miR-27 exerts protective effects against OA.