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  • Title: Circ_0020093 Overexpression Alleviates Interleukin-1 Beta-induced Inflammation, Apoptosis and Extracellular Matrix Degradation in Human Chondrocytes by Targeting the miR-181a-5p/ERG Pathway.
    Author: Zhu J, Guo Y.
    Journal: Immunol Invest; 2022 Aug; 51(6):1660-1677. PubMed ID: 35012421.
    Abstract:
    Osteoarthritis (OA) is a well-known chronic degenerative joint disease, with multiple changes in the phenotype of chondrocytes. Circular RNAs (circRNAs) have been shown to be involved in various human diseases, including OA. The purpose of this study was to determine the role of circ_0020093 in OA pathological changes in vitro. C28/I2 cells were treated with interleukin-1 beta (IL-1β) to mimic OA pathological conditions. The expression levels of circ_0020093, miR-181a-5p and ETS-related gene (ERG) mRNA were measured by quantitative real-time PCR (qRT-PCR). For functional analyses, cell proliferative capacity was detected using EdU assay and CCK-8 assay. Inflammatory response was assessed by determining the release of pro-inflammatory factors using ELISA kits. Cell apoptosis was examined by flow cytometry assay. The levels of apoptosis-related proteins and extracellular matrix (ECM)-associated proteins were assessed by Western blot. The binding relationship between miR-181a-5p and circ_0020093 or ERG was confirmed by RNA pull-down assay, dual-luciferase reporter assay or RIP assay. The expression level of circ_0020093 was decreased in IL-1β-treated C28/I2 cells. Circ_0020093 overexpression relieved inflammatory responses, cell apoptosis and ECM degradation in IL-1β-induced C28/I2 cells. Circ_0020093 directly targeted miR-181a-5p, and miR-181a-5p bound to the 3' -untranslated region (3'UTR) of ERG to regulate ERG expression. Circ_0020093 overexpression promoted the expression of ERG by sponging miR-181a-5p. Rescue experiments showed that miR-181a-5p overexpression or ERG knockdown could reverse the inhibitory effects of circ_0020093 overexpression on the pathological changes in IL-1β-induced C28/I2 cells. Circ_0020093 overexpression alleviated IL-1β-induced human chondrocyte inflammatory injury, apoptosis and ECM degradation by targeting miR-181a-5p/ERG pathway.
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