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MicroRNA-127-5p regulates osteopontin expression and osteopontin-mediated proliferation of human chondrocytes

机译:MicroRNA-127-5p调节骨桥蛋白的表达和骨桥蛋白介导的人类软骨细胞增殖

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摘要

The aim of this study was to determine the specific microRNA (miRNA) that regulates expression of osteopontin (OPN) in osteoarthritis (OA). The potential regulatory miRNAs for OPN messenger RNA (mRNA) were predicted by miRNA prediction programs. Among eight potential regulatory miRNAs, miR-220b, miR-513a-3p and miR-548n increased, while miR-181a, miR-181b, miR-181c, miR-181d and miR-127-5p decreased in OA patients. miRNA-127-5p mimics suppressed OPN production as well as the activity of a reporter construct containing the 3′-UTR of human OPN mRNA. In addition, mutation of miR-127-5p binding site in the 3′-UTR of OPN mRNA abolished miR-127-5p-mediated repression of reporter activity. Conversely, treatment with miR-127-5p inhibitor increased reporter activity and OPN production. Interestingly, miR-127-5p inhibited proliferation of chondrocytes through OPN. In conclusion, miRNA-127-5p is an important regulator of OPN in human chondrocytes and may contribute to the development of OA.
机译:这项研究的目的是确定骨关节炎(OA)中调节骨桥蛋白(OPN)表达的特异性microRNA(miRNA)。通过miRNA预测程序可以预测OPN信使RNA(mRNA)的潜在调控miRNA。在八种潜在的调节性miRNA中,OA患者中miR-220b,miR-513a-3p和miR-548n增加,而miR-181a,miR-181b,miR-181c,miR-181d和miR-127-5p减少。 miRNA-127-5p模拟物抑制了OPN的产生以及包含人OPN mRNA 3'-UTR的报告基因构建物的活性。此外,OPN mRNA 3'-UTR中miR-127-5p结合位点的突变消除了miR-127-5p介导的报告基因活性的抑制。相反,用miR-127-5p抑制剂治疗可增加报道分子活性和OPN产生。有趣的是,miR-127-5p通过OPN抑制软骨细胞的增殖。总之,miRNA-127-5p是人软骨细胞中OPN的重要调节剂,可能有助于OA的发展。

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