miR‑204‑5p inhibits the occurrence and development of osteoarthritis by targeting Runx2

Cao,Jiaqing; Han,Xinyou; Qi,Xin; Jin,Xiangyun; Li,Xiaolin

doi:10.3892/ijmm.2018.3811

miR‑204‑5p inhibits the occurrence and development of osteoarthritis by targeting Runx2

Authors:
- Jiaqing Cao
- Xinyou Han
- Xin Qi
- Xiangyun Jin
- Xiaolin Li
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Affiliations: Department of Orthopedic Surgery, The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200233, P.R. China
Published online on: August 7, 2018 https://doi.org/10.3892/ijmm.2018.3811
Pages: 2560-2568
Copyright: © Cao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

One of the hallmarks of osteoarthritis (OA) development is endochondral ossification, in which Runt‑related transcription factor‑2 (Runx2) is aberrantly expressed. Runx2 was previously identified to be regulated by microRNA‑204‑5p (miR‑204‑5p). The aim of the present study was to investigate the potential function of miR‑204‑5p regulating Runx2 during the development of OA and the underlying molecular mechanism. The expression levels of miR‑204‑5p and Runx2 were determined in tissue specimens. Rat OA models were established by transecting the anterior and posterior cruciate ligaments and removing the meniscus. Rats were treated with miR‑204‑5p agomir and miR‑204‑5p negative control (NC). All in vitro experiments were performed using rat primary chondrocytes and the SW‑1353 human bone chondrosarcoma cell line. It was identified that the expression of miR‑204‑5p was significantly decreased, whereas Runx2 was significantly increased, in human OA tissues compared with in non‑OA tissues, and levels were inversely associated with each other in primary chondrocytes and chondrosarcoma cells. Overexpression of miR‑204‑5p decreased the proliferation of chondrocytes and SW‑1353 cells. Using a luciferase reporter assay, Runx2 was identified to be a direct target of miR‑204‑5p in chondrocytes and overexpressed miR‑204‑5p altered the expression of collagens II, X and matrix metalloproteinase (MMP)‑1 and MMP‑13 in primary chondrocytes and SW‑1353 cells. Histological analysis revealed that miR‑204‑5p treatment ameliorated the OA‑like phenotype that is reflected by assessment of cartilage thickness and Mankin's score. Runx2 expression was gradually increased as the rats increased in age. At 10 weeks of miR‑204‑5p agomir treatment, altered expression levels of collagens II and X, cartilage oligomeric matrix protein fragment, aggrecan, MMP‑1 and MMP‑13 were observed in the treatment group compared with the NC group. In conclusion, the results of the present study indicated that miR‑204‑5p decreases chondrocyte proliferation and ameliorates the OA‑like phenotype in rats with surgically induced OA by targeting Runx2.

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