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Oleanolic acid mitigates interleukin‐1β‐induced chondrocyte dysfunction by regulating miR‐148‐3p‐modulated FGF2 expression
Author(s) -
Li Yuanli,
Nie Junlan,
Jiang Ping
Publication year - 2020
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.3169
Subject(s) - chondrocyte , viability assay , small interfering rna , microbiology and biotechnology , microrna , apoptosis , cell growth , signal transduction , fibroblast growth factor , biology , chemistry , transfection , cartilage , biochemistry , gene , receptor , anatomy
Background 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. Methods 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. Results 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. Conclusions 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.