Molecular Therapy: Nucleic Acids (Jun 2017)
Emerging Roles of circRNA Related to the Mechanical Stress in Human Cartilage Degradation of Osteoarthritis
Abstract
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.
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