circRNA.33186 Contributes to the Pathogenesis of Osteoarthritis by Sponging miR-127-5p
circRNA.33186 Contributes to the Pathogenesis of Osteoarthritis by Sponging miR-127-5p
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circRNA.33186 通过海绵 miR-127-5p 促进骨关节炎的发病机制
DOI：
10.1016/j.ymthe.2019.01.006
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发表时间：
2019-03-06
影响因子：
12.4
通讯作者：
Zhu, Lei
中科院分区：
文献类型：
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作者：
Zhou, Zhi-bin;Huang, Gao-xiang;Zhu, Lei
骨关节炎是最常见的与年龄相关的关节疾病，以慢性炎症、进行性关节软骨破坏和软骨下骨硬化为特征。越来越多的证据表明，CircRNAs在各种疾病中起着关键作用，但CircRNAs在骨性关节炎中的作用仍不清楚。在这里，我们展示了CircRNA。在IL-1β处理的软骨细胞和不稳定的内侧半月板诱导的骨关节炎小鼠模型的软骨组织中，33186显著上调。CircRNA的敲除。33186使合成代谢因子(II型胶原)表达增加，分解代谢因子(MMP13)表达降低。CircRNA的敲除。33186还能促进IL-1β诱导的软骨细胞增殖和抑制细胞凋亡。使CircRNA沉默。33186体内给药可明显减轻二甲双吗啉诱导的骨性关节炎。机制研究表明，CircRNA。33186直接与miR-127-5p结合，抑制miR-127-5p，从而增加基质金属蛋白酶-13的表达，参与骨关节炎的发病。综上所述，我们的发现证明了CircRNA的基本作用。33186的研究进展，为骨性关节炎的治疗提供了潜在的药物靶点。
Osteoarthritis (OA), the most prevalent age-related joint disorder, is characterized by chronic inflammation, progressive articular cartilage destruction, and subchondral bone sclerosis. Accumulating evidences indicate that circularRNAs(circRNAs) play a critical role in various diseases, but the function of circRNAs in OA remains largely unknown. Here we showed that circRNA. 33186 was significantly upregulated in IL-1 beta)-treated chondrocytes and in cartilage tissues of a destabilized medial meniscus (DMM)-induced OA mouse model. Knockdown of circRNA. 33186 increased anabolic factor (type II collagen) expression and decreased catabolic factor (MMP-13) expression. Knockdown of circRNA. 33186 also promoted proliferation and inhibited apoptosis in IL-1 beta-treated chondrocytes. Silencing of circRNA. 33186 in vivo markedly alleviated DMM-induced OA. Mechanistic study showed that circRNA. 33186 directly binds to and inhibits miR-127-5p, thereby increasing MMP-13 expression, and contributes to OA pathogenesis. Taken together, our findings demonstrated a fundamental role of circRNA. 33186 inOAprogression and provide a potential drug target in OA therapy.