PMID:
J Gene Med. 2020 Feb 6:e3169. Epub 2020 Feb 6. PMID: 32028542
Abstract Title:
Oleanolic acid mitigates interleukin-1β-induced chondrocyte dysfunction by regulating miR-148-3p-modulated FGF2 expression.
Abstract:
BACKGROUND: microRNAs (miRs)-mediated post-transcriptional repression has been reported in the process of chondrocyte dysfunction. The present study is aimed to investigate the molecular mechanisms underlying in oleanolic acid (OLA)-prevented interleukin-1β (IL-1β)-induced chondrocyte dysfunction via the miR-148-3p/FGF2 signaling pathway.METHODS: Candidate miRs were filtrated using miR microarray assays in chondrocyte with or without IL-1β stimulation. Gene expression of candidate miRs and protein expression of FGF2 were analyzed using RT-qPCR and western blotting, respectively. Cell growth was evaluated using CCK8 assays. Cell apoptosis was detected using Annexin V-FITC double staining.RESULTS: Treatment with OLA counteracted IL-1β-evoked chondrocyte growth inhibition, apoptosis, caspase3 production, MDA and 8-OHdG release. Additionally, FGF2 protein expression levels elevated by IL-1β were down-regulated by OLA and miR-148-3p mimics transfection. 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.CONCLUSIONS: Our present findings expounded a protective effect of OLA on IL-1β-induced chondrocyte dysfunction, and a novel signal cascade the miR-148-3p/FGF2 signaling pathway might be a potential therapeutic target of OLA to prevent the progression of osteoarthritis (OA).
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