MicroRNA‐30a promotes extracellular matrix degradation in articular cartilage via downregulation of Sox9

Cell Proliferation - Tập 49 Số 2 - Trang 207-218 - 2016
Tingjie Chang1,2, Jie Xie2, Hongzhuo Li1, Dong Li1, Ping Liu2,3, Yihe Hu2
1Department of Orthopedics Peace Hospital of Changzhi Medical College Changzhi Shanxi 046000 China
2Department of Orthopedics Xiangya Hospital of Central South University Changsha Hunan 410008 China
3Department of oncology Peace Hospital of Changzhi Medical College Changzhi 046000 PR China

Tóm tắt

AbstractObjectivesSox9 has recently been reported to be a key mediator during cartilage degradation in osteoarthritis (OA). Our aim was to clarify the role of microRNA‐30a (miR‐30a) and its target gene Sox9 in regulation of extracellular matrix (ECM) degradation in OA.Materials and methodsExpression of miR‐30a in cartilage tissues and in primary chondrocytes from healthy and OA donors, was determined by real‐time PCR, and levels of Sox9 mRNA and protein were analyzed by real‐time PCR and western blotting, respectively. Subsequently, the target of miR‐30a was predicted by bioinformatics and confirmed using a luciferase assay. Expression of ECM‐related genes was determined by tissue‐specific staining, immunofluorescence, real‐time PCR, and western blotting. The role of miR‐30a in OA was examined in vivo using a collagenase‐induced OA rat model.ResultsmiR‐30a was significantly upregulated and Sox9 was downregulated in primary chondrocytes from cartilage taken from OA donors compared to healthy controls. We showed that miR‐30a specifically bound to the 3′ UTR of Sox9, and overexpression of miR‐30a downregulated expression levels of Sox9, proteoglycan aggrecan, and Col II compared to those induced by small interfering RNA transfection to knockdown Sox9. miR‐30a inhibition reversed the effects of ECM degradation in vitro and in vivo.ConclusionsmiR‐30a acts as a virulence MRA in OA, promoting ECM degradation by targeting Sox9 and by modulating activity of its downstream effectors Col II and proteoglycan aggrecan.

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Cell Proliferation

Tập 49 Số 2

207-218

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