Emerging Roles of circRNA Related to the Mechanical Stress in Human Cartilage Degradation of Osteoarthritis.
Emerging Roles of circRNA Related to the Mechanical Stress in Human Cartilage Degradation of Osteoarthritis.
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与机械应力相关的 circRNA 在骨关节炎人类软骨退化中的新作用
DOI：
10.1016/j.omtn.2017.04.004
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发表时间：
2017-06-16
期刊：
影响因子：
--
通讯作者：
Ao Y
中科院分区：
文献类型：
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作者：
Liu Q;Zhang X;Hu X;Yuan L;Cheng J;Jiang Y;Ao Y
环状rna （circRNAs）参与各种疾病的发展；然而，关于环状rna在骨关节炎（OA）中的作用的知识有限。本研究旨在鉴定OA影响的不同区域中circRNA的表达，并探讨机械应力相关circRNA （circRNAs- msr）在软骨中的功能。生物信息学用于预测软骨中环状rna和mrna的相互作用。在体外进行circrna - msr的功能丧失实验。在受损软骨和完整软骨中，共有104个环状rna差异表达。在这些环状rna中，受损组织中分别有44个和60个表达上调和下调。机械应力作用下软骨细胞中circRNA-MSR表达增加。用小干扰RNA沉默circRNAs-MSR，敲低circRNAs-MSR可抑制肿瘤坏死因子α (TNF-α)的表达，增加细胞外基质（ECM）的形成。我们的研究结果表明，circRNAs-MSR调节TNF-α表达并参与软骨细胞ECM降解过程。我们提出，抑制circRNAs-MSR可以抑制软骨细胞ECM的降解，敲低circRNAs-MSR可能是OA的潜在治疗靶点。
Circular RNAs (circRNAs) are involved in the development of various diseases; however, knowledge on circRNAs in osteoarthritis (OA) is limited. This study aims to identify circRNA expression in different regions affected by OA and to explore the function of mechanical stress-related circRNAs (circRNAs-MSR) in cartilage. Bioinformatics was employed to predict the interaction of circRNAs and mRNAs in the cartilage. Loss-of-function experiments for circRNAs-MSR were performed in vitro. A total of 104 circRNAs were differentially expressed in damaged versus intact cartilage. Of these circRNAs, 44 and 60 were upregulated and downregulated, respectively, in the damaged tissue. circRNA-MSR expression increased under mechanical stress in chondrocytes. circRNAs-MSR were silenced using small interfering RNA, and knockdown of circRNAs-MSR could suppress tumor necrosis factor alpha (TNF-α) expression and increase extracellular matrix (ECM) formation. Our results demonstrated that circRNAs-MSR regulated TNF-α expression and participated in the chondrocyte ECM degradation process. We propose that the inhibition of circRNAs-MSR could inhibit the degradation of chondrocyte ECM and knockdown of circRNAs-MSR could be a potential therapeutic target for OA.