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.

Objective. Long noncoding RNAs (lncRNAs) play crucial regulatory roles in diverse biologic processes, but knowledge of lncRNAs in osteoarthritis (OA) is limited. The aim of this study was to identify lncRNA expression in articular cartilage and to explore the function of cartilage injury-related lncRNAs (lncRNA-CIR) in OA.Methods. To identify lncRNAs specifically expressed in OA cartilage, we compared the expression of lncRNAs in OA cartilage with that in normal cartilage using microarray and quantitative polymerase chain reaction (qPCR) analyses. In OA cartilage, lncRNA-CIR was specifically, differentially, and highly expressed. The function of lncRNA-CIR was determined by silencing and overexpression in vitro. Extracellular matrix (ECM)-related molecules were detected by qPCR, Western blot, and immunofluorescence analyses.Results. Up to 152 lncRNAs were found to be differentially expressed (>8-fold) in OA and normal cartilage (82 lncRNAs more highly expressed and 70 less highly expressed in OA cartilage than in normal cartilage). A specific differentially expressed lncRNA-CIR was selected according to the results of the higher expression in OA cartilage and OA chondrocytes. The expression of lncRNA-CIR increased in chondrocytes with in vitro treatment with interleukin-1␤ and tumor necrosis factor ␣. Silencing of lncRNA-CIR by small interfering RNA promoted the formation of collagen and aggrecan and reduced the expression of matrixdegrading enzymes, such as MMP13 and ADAMTS5. The expression of collagen and aggrecan was reduced, whereas the expression of matrix-degrading enzymes was increased, after overexpression of lncRNA-CIR.Conclusion. The results indicate that lncRNA-CIR contributes to ECM degradation and plays a key role in the pathogenesis of OA. We propose that lncRNA-CIR could be used as a potential target in OA therapy.Osteoarthritis (OA) is a degenerative joint disease characterized by degradation of articular cartilage, thickening of subchondral bone, and formation of osteophytes (1). OA is associated with age-related loss of homeostatic balance. Cartilage cellularity in OA is reduced by chondrocyte death, and chondrocytes are stimulated by cytokines and growth factors to a catabolic and abnormal differentiation that leads to degradation of the extracellular matrix (ECM) (2-5). Degradation of the ECM is complicated, for it involves genetic, developmental, biochemical, and biomechanical factors. The molecular mechanisms involved in the maintenance of articular cartilage have been characterized in order to develop new therapeutic interventions (6,7).The human transcriptome comprises not only protein-coding messenger RNAs (mRNAs), but also a large amount of non-protein-coding transcripts that have structural, regulatory, or unknown functions (8). Although studies of small noncoding RNAs (microRNAs, consisting of 18-200 nucleotides) have dominated the field of RNA biology in recent years (9-11), multiple studies have indicated that promising new molecules, namely, long noncoding RNAs (lncRNAs),

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