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  • Title: Circ_0008365 Suppresses Apoptosis, Inflammation and Extracellular Matrix Degradation of IL-1β-treated Chondrocytes in Osteoarthritis by Regulating miR-324-5p/BMPR2/NF-κB Signaling Axis.
    Author: Zhang Z, Zhao T, Xu H, Wu X.
    Journal: Immunol Invest; 2022 Aug; 51(6):1598-1611. PubMed ID: 35172669.
    Abstract:
    BACKGROUND: Recent studies have revealed that circular RNAs (circRNAs) play crucial roles in the progression of osteoarthritis (OA). This study aimed to investigate the biological function and regulatory mechanism of circ_0008365 in OA. METHODS: OA cell model in vitro was established in chondrocytes by treatment with Interleukin-1β (IL-1β). The levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The expression levels of circ_0008365, microRNA-324-5p (miR-324-5p) and bone morphogenetic protein type 2 receptor (BMPR2) were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis was assessed using flow cytometry and caspase3 activity assays. The protein expression was determined via a western blot assay. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and RNA pull-down assays were used to analyze the correlation between targets. RESULTS: IL-1β level and miR-324-5p expression were increased, while circ_0008365 was downregulated in OA patients. IL-1β treatment-induced cell apoptosis, inflammation and extracellular matrix (ECM) degradation in chondrocytes. Besides, circ_0008365 overexpression partly relieved IL-1β-induced cell damage in chondrocytes. Circ_0008365 could interact with miR-324-5p, and BMPR2 was a downstream target of miR-324-5p. Overexpression of miR-324-5p or BMPR2 knockdown partly overturned the inhibiting effect of circ_0008365 on cell damage in IL-1β-induced chondrocytes. In addition, circ_0008365 inactivated NF-κB pathway via regulating miR-324-5p/BMPR2 axis. CONCLUSION: Circ_0008365 reduced IL-1β-induced cell damage in chondrocytes via inactivating NF-κB signaling pathway and regulating miR-324-5p/BMPR2 axis.Abbreviations OA: osteoarthritis; BMPR2: bone morphogenetic protein type 2 receptor.
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