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Circular RNA CircDHRS3 Aggravates IL-1β-induced ECM Degradation, Apoptosis, and Inflammatory Response via Mediating MECP2 Expression

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Abstract

Previous studies have reported that circular RNA hsa_circ_0010024 (circDHRS3), microRNA (miR)-193a-3p, and Methyl CpG binding protein 2 (MECP2) are unconventionally expressed in osteoarthritis (OA) cartilage samples. However, the regulatory mechanisms among circDHRS3, miR-193a-3p, and MECP2 in OA pathogenesis are unclear. Changes of circDHRS3, miR-193a-3p, and MECP2 mRNA were detected by qRT-PCR. Several protein levels were evaluated using western blotting. Cell proliferation was analyzed by 5-Ethynyl-2’-deoxyuridine (EdU) and cell counting assays. Cell apoptosis was determined by flow cytometry assay. Detection of pro-inflammatory cytokines was conducted using ELISA. The relationship between circDHRS3 or MECP2 and miR-193a-3p was validated by dual-luciferase reporter assay. We verified that circDHRS3 and MECP2 were overexpressed in OA cartilage samples, whereas miR-193a-3p was downregulated. CircDHRS3 silencing weakened IL-1β-induced chondrocyte cartilage extracellular matrix (ECM) degradation, apoptosis, and inflammatory response. CircDHRS3 adsorbed miR-193a-3p to modulate MECP2 expression. Also, silencing of miR-193a-3p impaired circDHRS3 silencing-mediated suppression on IL-1β-induced chondrocyte injury. Also, MECP2 overexpression alleviated miR-193a-3p mimic-mediated inhibition on IL-1β-prompted chondrocyte injury. CircDHRS3 silencing reduced MECP2 expression via sponging miR-193a-3p, thereby weakening IL-1β-induced chondrocyte ECM degradation, apoptosis, and inflammatory response.

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DATA AVAILABILITY

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Xuzhou Third People’s Hospital, Affiliated Xuzhou Hospital of Jiangsu University, No.131, Huancheng Road, Gulou, Xuzhou, 221005, Jiangsu, China

    Xiao Ouyang, Yunzhi Ding, Li Yu, Feng Xin, Xiaowei Yang, Xingyong Liu & Songming Tong

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  3. Li Yu
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Contributions

Xiao Ouyang designed and supervised the study. Xiao Ouyang and Li Yu conducted the experiments and drafted the manuscript. Feng Xin and Xiaowei Yang collected and analyzed the data. Xingyong Liu contributed the methodology. Songming Tong operated the software and edited the manuscript. All authors reviewed the manuscript.

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Correspondence to Xiao Ouyang.

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The research was approved by the Ethics Committee of Xuzhou Third People’s Hospital, Affiliated Xuzhou Hospital of Jiangsu University and follows the tenets of the Declaration of Helsinki.

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Ouyang, X., Ding, Y., Yu, L. et al. Circular RNA CircDHRS3 Aggravates IL-1β-induced ECM Degradation, Apoptosis, and Inflammatory Response via Mediating MECP2 Expression. Inflammation 46, 1670–1683 (2023). https://doi.org/10.1007/s10753-023-01832-3

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