Circular RNA Related to the Chondrocyte ECM Regulates MMP13 Expression by Functioning as a MiR-136 ‘Sponge’ in Human Cartilage Degradation

• Published in: Scientific reports 2016-03, Vol.6 (1), p.22572-22572, Article 22572
• Main Authors: Liu, Qiang, Zhang, Xin, Hu, Xiaoqing, Dai, Linghui, Fu, Xin, Zhang, Jiying, Ao, Yingfang
• Format: Article
• Language: English
• Subjects: 13/51; 38/109; 38/89; 692/4023/1670/407; 692/4023/1671/1354; Aged; Bioinformatics; Cartilage (articular); Cartilage diseases; Cartilage, Articular - pathology; Chondrocytes; Chondrocytes - drug effects; Chondrocytes - metabolism; Circular RNA; Collagenase 3; Extracellular matrix; Extracellular Matrix - metabolism; Female; Gene Expression Profiling; Humanities and Social Sciences; Humans; Interleukin 1; Interleukin-1 - pharmacology; Knee; Male; Matrix Metalloproteinase 13 - metabolism; MicroRNAs - metabolism; Middle Aged; multidisciplinary; Osteoarthritis; RNA - genetics; RNA - physiology; Science; Science (multidisciplinary); siRNA; Tumor Necrosis Factor-alpha - pharmacology; Up-Regulation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep22572

Circular RNAs (circRNAs) are involved in the development of various diseases, but there is little knowledge of circRNAs in osteoarthritis (OA). The aim of study was to identify circRNA expression in articular cartilage and to explore the function of chondrocyte extracellular matrix (ECM)-related circRNAs (circRNA-CER) in cartilage. To identify circRNAs that are specifically expressed in cartilage, we compared the expression of circRNAs in OA cartilage with that in normal cartilage. Bioinformatics was employed to predict the interaction of circRNAs and mRNAs in cartilage. Loss-of-function and rescue experiments for circRNA-CER were performed in vitro . A total of 71 circRNAs were differentially expressed in OA and normal cartilage. CircRNA-CER expression increased with interleukin-1 and tumor necrosis factor levels in chondrocytes. Silencing of circRNA-CER using small interfering RNA suppressed MMP13 expression and increased ECM formation. CircRNA-CER could compete for miR-136 with MMP13. Our results demonstrated that circRNA-CER regulated MMP13 expression by functioning as a competing endogenous RNA (ceRNA) and participated in the process of chondrocyte ECM degradation. We propose that circRNA-CER could be used as a potential target in OA therapy.