Abstract
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.
Highlights
Circular RNAs are a large class of non-coding RNAs that exist ubiquitously in the cytoplasm of eukaryotic cells[8,9]; these endogenous RNAs are characterized by a stable structure and high tissue-specific expression[10]
We initially identified a new circRNA involved in the process of cartilage injury and proposed that circRNA-CER could be used as a potential target in OA therapy
Many studies on OA have focused on the epigenetic regulation of its pathogenesis and potential targets for therapy, including microRNAs and long noncoding RNAs
Summary
Circular RNAs (circRNAs) are a large class of non-coding RNAs that exist ubiquitously in the cytoplasm of eukaryotic cells[8,9]; these endogenous RNAs are characterized by a stable structure and high tissue-specific expression[10]. It was demonstrated that circRNAs are involved in the development of several types of diseases, such as atherosclerosis and nervous system disorders[14,15,16]. The role of circRNAs in cartilage and their overall contribution to OA pathogenesis are still unknown. We identified a small number of circRNAs that are up- or down-regulated in OA versus normal cartilage. These circRNAs may exhibit an important function in cartilage injury and OA development and progression. We examined the functions and mechanisms of circRNAs in OA pathogenesis. We initially identified a new circRNA involved in the process of cartilage injury and proposed that circRNA-CER could be used as a potential target in OA therapy
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