MiR-29a and MiR-140 Protect Chondrocytes against the Anti-Proliferation and Cell Matrix Signaling Changes by IL-1beta

Guofu Yang; Xianghui Li; Zhilei Zhen; Guodong Tang; Chong Zheng

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자료유형: 학술저널

저자정보: Guofu Yang (Harbin Medical University) Xianghui Li (Harbin Medical University) Zhilei Zhen (Harbin Medical University) Guodong Tang (Harbin Medical University) Chong Zheng (Harbin Medical University)

저널정보: 한국분자세포생물학회 Molecules and Cells Molecules and Cells 제39권 제2호

발행연도: 2016.2

수록면: 103 - 110 (8page)

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As a degenerative joint disease, osteoarthritis (OA) constitutes a major cause of disability that seriously af-fects the quality of life of a large population of people worldwide. However, effective treatment that can successfully reverse OA progression is lacking until now. The present study aimed to determine whether two small non-coding RNAs miR-29a and miR-140, which are significantly down-regulated in OA, can be applied together as potential therapeutic targets for OA treatment. MiRNA synergy score was used to screen the miRNA pairs that potentially synergistically regulate OA. An in vitro model of OA was established by treating murine chondrocytes with IL-1?. Transfection of miR-29a and miR-140 via plasmids was investigated on chondrocyte proliferation and expression of nine genes such as ADAMTS4, ADAMTS5, ACAN, COL2A1, COL10A1, MMP1, MMP3, MMP13 and TIMP metallopeptidase inhibitor 1 (TIMP1). Western blotting was used to determine the protein expression level of MMP13 and TIMP1, and ELISA was used to detect the content of type II collagen. Combined use of miR-29a and miR-140 successfully reversed the destructive effect of IL-1? on chondrocyte proliferation, and notably affected the MMP13 and TIMP1 gene expression that regulates extracellular matrix. Although co-transfection of miR-29a and miR-140 did not show a synergistic effect on MMP13 protein expression and type II collagen release, but both of them can significantly suppress the protein abun-dance of MMP13 and restore the type II collagen release in IL-1? treated chondrocytes. Compared with single miRNA transfection, co-transfection of both miRNAs exceedingly abrogated the suppressed the protein production of TIMP1 caused by IL-1?, thereby suggesting potent synergistic action. These results provided novel insights into the important function of miRNAs' collaboration in OA pathological development. The reduced MMP13, and enhanced TIMP1 protein production and type II collagen release also implies that miR-29a and miR-140 combination treatment may be a possible treatment for OA.

#microRNA #miR-29a #miR-140 #osteoarthritis

참고문헌 (33)

참고문헌 신청

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Diaz-Prado, S. / 2012 / Characterization of microRNA expression profiles in normal and osteoarthritic human chondrocytes / BMC Musculoskelet Disord 13:144

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Gosset, M. / 2008 / Primary culture and phenotyping of murine chondrocytes / Nat. Protoc 3:1253~1260

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