miR-31-5p靶向Notch1调节骨关节炎软骨细胞增殖和凋亡的作用

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摘要目的明确miR-31-5p在骨关节炎软骨细胞中的作用。方法采用Hulth法进行大鼠骨关节炎造模，并分离原代软骨细胞，白细胞介素(interleukin，IL)-1β诱导体外模型，检测miR-31-5p的表达变化；进一步通过在线数据库预测miR-31-5p靶点并验证，细胞增殖检测试剂盒(cell counting kit-8，CCK-8)和流式细胞术检测miR-31-5p对原代软骨细胞增殖和凋亡的影响。结果骨关节炎大鼠中miR-31-5p表达下调；miR-31-5p mimics促进软骨细胞增殖，而miR-31-5p inhibitor诱导软骨细胞凋亡增加；此外，miR-31-5p inhibitor促进IL-6和基质金属蛋白酶13(matrix metalloprotein，MMP-13)表达增加；荧光素酶报告基因实验证实Notch1是miR-31-5p的直接靶点，Notch1过表达质粒会部分抵消miR-31-5p mimics对软骨细胞的增殖保护作用。结论 miR-31-5p下调表达介导骨关节炎软骨细胞增殖受限和凋亡发生，可能参与骨关节炎的发病。

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	文良华 1
	陈世华 1
	寿折星 2

关键词 ：骨关节炎, 软骨细胞, miR-31-5p, Notch1

Abstract：Objective To identify the effects of miR-31-5p on osteoarthritis chondrocytes.Methods Osteoarthritis models of rats were established according to Hulth method，and primary chondrocytes were isolated and treated by interleukin 1β (IL-1β).The expression of miR-31-5p was evaluated by qRT-PCR.The potential target of miR-31-5p was predicted by TargetScanHuman database，and verified by luciferase reporter assay.Effects of miR-31-5p on proliferation and apoptosis of primary chondrocytes were determined by Cell Counting Kit-8 (CCK-8) and Flow Cytometry.Results The expression of miR-31-5p was downregulated in osteoarthritis models of rats.miR-31-5p mimics promoted proliferation of chondrocytes，and miR-31-5p inhibitor led to apoptosis of chondrocytes.Moreover，miR-31-5p inhibitor promoted expression of IL-6 and matrix metalloprotein 13 (MMP-13).Further investigation revealed Notch1 was the direct target of miR-31-5p，and Notch1 overexpression partially limited the protective role of miR-31-5p mimics in chondrocytes.Conclusion The downregulated miR-31-5p mediated apoptosis and limited proliferation of chondrocytes in osteoarthritis，which might contribute to pathogenesis of osteoarthritis.

Key words： osteoarthritis chondrocytes miR-31-5p Notch1

基金资助:中医药科研项目(ZY2019Q002)

作者简介: 文良华(1977－ )，男，主治医师，荆州市公安县中医院骨科，434300。

引用本文:

文良华 1，陈世华 1，寿折星 2. miR-31-5p靶向Notch1调节骨关节炎软骨细胞增殖和凋亡的作用[J]. 实用骨科杂志, 2020, 26(5): 421-427.
Wen Lianghua 1，Chen Shihua 1，Shou Zhexing 2. Effects of miR-31-5p on Proliferation and Apoptosis of Osteoarthritis Chondrocytes by Targeting Notch1. sygkzz, 2020, 26(5): 421-427.

链接本文:

http://www.sygkzz.com/CN/ 或 http://www.sygkzz.com/CN/Y2020/V26/I5/421

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