miR‑17‑5p and miR‑19b‑3p prevent osteoarthritis progression by targeting EZH2

Li,Yong; Yuan,Fangchang; Song,Yuxi; Guan,Xiliang

doi:10.3892/etm.2020.8887

miR‑17‑5p and miR‑19b‑3p prevent osteoarthritis progression by targeting EZH2

Authors:
- Yong Li
- Fangchang Yuan
- Yuxi Song
- Xiliang Guan
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Affiliations: Department of Orthopaedic Surgery, The People's Hospital of Rizhao, Rizhao, Shandong 276800, P.R. China, Department of Hand Surgery, The People's Hospital of Rizhao, Rizhao, Shandong 276800, P.R. China
Published online on: June 12, 2020 https://doi.org/10.3892/etm.2020.8887
Pages: 1653-1663
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteoarthritis (OA) is a joint disease caused by a variety of factors, including aging, obesity and trauma. MicroRNAs (miRNAs) have been reported to be crucial regulators during OA progression. The present study aimed to investigate the role of miR‑17‑5p and miR‑19b‑3p during OA development. Interleukin (IL)‑1β‑treated chondrocytes were used to mimic OA in vitro. The expression levels of miR‑17‑5p and enhancer of zeste homolog 2 (EZH2) were measured in cartilage tissues and chondrocytes using reverse transcription‑quantitative PCR or western blotting. Apoptosis was assessed by flow cytometry. The protein expression levels of extracellular matrix (ECM)‑associated genes were detected by western blotting. The binding sites between miR‑17‑5p or miR‑19b‑3p and EZH2 were predicted using the MicroT‑CDS online database and verified using dual‑luciferase reporter and RIP assays. miR‑17‑5p expression was downregulated, whereas EZH2 expression was upregulated in OA cartilage tissues and IL‑1β‑induced chondrocytes compared with that in the control tissues and cells. miR‑17‑5p mimics inhibited IL‑1β‑induced apoptosis and ECM degradation in chondrocytes. EZH2 was the target of miR‑17‑5p and miR‑19b‑3p in chondrocytes, and enhanced apoptosis and ECM degradation in IL‑1β‑stimulated chondrocytes. Rescue experiments revealed that miR‑17‑5p or miR‑19b‑3p mimic‑induced inhibition of OA progression was reversed by EZH2 overexpression. In conclusion, miR‑17‑5p and miR‑19b‑3p inhibited OA progression by targeting EZH2, which may serve as a potential therapeutic target for OA.

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