Oleanolic acid mitigates interleukin-1β-induced chondrocyte dysfunction by regulating miR-148-3p-modulated FGF2 expression.

Abstract

microRNA (miR)-mediated post-transcriptional repression has been reported in the process of chondrocyte dysfunction. The present study aimed to investigate the molecular mechanisms underlying in oleanolic acid (OLA)-prevented interleukin (IL)-1β-induced chondrocyte dysfunction via the miR-148-3p/fibroblast growth factor-2 (FGF-2) signaling pathway. Candidate miRs were filtrated using miR microarray assays in chondrocytes with or without IL-1β stimulation. Gene expression of candidate miRs and protein expression of FGF2 were analyzed using a quantitative reverse transcriptase-polymerase chain reaction and western blotting, respectively. Cell growth was evaluated using cell counting kit-8 assays. Cell apoptosis was detected using Annexin V-fluorescein isothiocyanate double staining. Treatment with OLA counteracted IL-1β-evoked chondrocyte growth inhibition, apoptosis, caspase3 production, and release of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine. Additionally, FGF2 protein expression levels elevated by IL-1β were down-regulated by OLA and transfection with miR-148-3p mimics. IL-1β-induced down-regulation of miR-148-3p in chondrocytes was evaluated by OLA administration. Bioinformatics algorithms and experimental measurements indicated that FGF2 might be a direct target of miR-148-3p. miR-148-3p mimics exhibited equal authenticity of OLA to protect against IL-1β-induced chondrocyte dysfunction. Our present findings highlight a protective effect of OLA on IL-1β-induced chondrocyte dysfunction, and a novel signal cascade comprising the miR-148-3p/FGF2 signaling pathway might be a potential therapeutic target of OLA with respect to preventing the progression of osteoarthritis.