Overexpression of microRNA‑210 promotes chondrocyte proliferation and extracellular matrix deposition by targeting HIF‑3α in osteoarthritis

Li,Zhifu; Meng,Dongdong; Li,Guangheng; Xu,Jianzhong; Tian,Ke; Li,Yu

doi:10.3892/mmr.2016.4878

Overexpression of microRNA‑210 promotes chondrocyte proliferation and extracellular matrix deposition by targeting HIF‑3α in osteoarthritis

Authors:
- Zhifu Li
- Dongdong Meng
- Guangheng Li
- Jianzhong Xu
- Ke Tian
- Yu Li
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Affiliations: Department of Orthopedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: February 5, 2016 https://doi.org/10.3892/mmr.2016.4878
Pages: 2769-2776

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Abstract

The present study aimed to determine the effect of microRNA (miR)‑210 on osteoarthritis (OA). The expression levels of miR‑210, type I and X collagen (COL1A1 and COL10A1) and matrix metallopeptidase 13 (MMP13) in OA and normal chondrocytes were determined using reverse transcription‑quantitative polymerase chain reaction analysis. The OA chondrocytes were transfected with an miRNA precursor for miR‑210 or a negative control. After 3, 7, 14 and 21 days, the expression levels of miR‑210 were examined, the proliferation of the OA chondrocytes were determined using an XTT assay and the protein levels of Ki67 and HIF‑3α were analyzed by Western blotting. After 21 days, the mRNA and protein levels of COL1A1, COL10A1 and MMP13 were analyzed. Th present study demonstrated that the expression levels of miR‑210 and COL1A1 were lower, and the expression levels of COL10A1 and MMP13 were higher in the OA chondrocytes, compared with the levels of expression in the normal chondrocytes. Overexpression of miR‑210 significantly promoted the proliferation of OA chondrocytes and induced the protein expression of Ki67. In addition, miR‑210 overexpression markedly increased the expression of COL1A1 expression, but decreased the expression levels of COL10A1 and MMP13. A luciferase reporter assay confirmed the direct interaction between miR‑210 and hypoxia‑inducible factor (HIF)‑3α. miR‑210 did not alter the mRNA expression of HIF‑3α, however, it suppressed the protein expression of HIF‑3α. Additionally, HIF‑3α knockdown significantly promoted OA chondrocyte proliferation and increased the mRNA levels of COL1A1, whereas it decreased the mRNA levels of COL10A1 and MMP13. The results of the present study suggested that miR‑210 may be a negative regulator of the progression of OA, which increases chondrocyte proliferation and prompts extracellular matrix deposition by directly targeting HIF‑3α.

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