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  • Title: microRNA-138 induces cell survival and reduces WNT/β-catenin signaling of osteoarthritis chondrocytes through NEK2.
    Author: Xu W, Gao P, Zhang Y, Piao L, Dong D.
    Journal: IUBMB Life; 2019 Sep; 71(9):1355-1366. PubMed ID: 31034758.
    Abstract:
    Osteoarthritis (OA) is a degenerative joint disease characterized by joint pain, stiffness, and function degeneration with high incidence. Recent studies have been inspired based on the association between microRNAs (miRs) and therapeutic research of OA. Hence, the present study evaluates the effects of miR-138 on chondrocyte proliferation, differentiation, and apoptosis through the WNT/β-catenin signaling pathway in mice with OA by binding to NIMA-related kinase 2 (NEK2). Appropriate dataset was selected from the Gene Expression Omnibus database, and differentially expressed genes and potential miRNAs that could regulate NEK2 were explored. A mouse model of OA was established. The expressions of miR-138, NEK2, β-catenin, GSK3β, Bcl-2, Bcl-2-associated X protein (Bax), p53, MMP-13, Col2, and Aggrecan and the phosphorylation levels of β-catenin were determined by the reverse transcription quantitative polymerase chain reaction and Western blot analysis. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and flow cytometry were employed to detect cell proliferation and apoptosis, respectively. The potential functional role of NEK2 was revealed to be related to the WNT/β-catenin signaling pathway, and miR-138 was the putative regulator of NEK2. miR-138 expression was downregulated while expressions of NEK2 and β-catenin as well as the phosphorylation levels of β-catenin were upregulated in mice with OA. The chondrocytes treated with miR-138 mimic and siRNA-NEK2 exhibited reduced expressions of NEK2, β-catenin, MMP-13, Bax, and p53 and elevated expressions of Col2, Aggrecan, and Bcl-2 as well as phosphorylation levels of β-catenin along with enhanced chondrocytes' proliferation and suppressed cell apoptosis. Overexpression of miR-138 induces cell survival and reduces WNT/β-catenin signaling of OA chondrocytes through NEK2. © 2019 IUBMB Life, 71(9):1355-1366, 2019.
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