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

Inflammation. 2023 Oct;46(5):1670-1683. doi: 10.1007/s10753-023-01832-3. Epub 2023 Jun 21.

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.

Keywords: IL-1β; MECP2; OA; circDHRS3; miR-193a-3p.

MeSH terms

  • Apoptosis
  • Cartilage / metabolism
  • Chondrocytes / metabolism
  • Humans
  • Interleukin-1beta / metabolism
  • Interleukin-1beta / pharmacology
  • Methyl-CpG-Binding Protein 2 / genetics
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Osteoarthritis* / pathology
  • RNA, Circular / genetics
  • RNA, Circular / metabolism

Substances

  • MicroRNAs
  • RNA, Circular
  • Methyl-CpG-Binding Protein 2
  • Interleukin-1beta