Knockdown of Circ_SLC39A8 protects against the progression of osteoarthritis by regulating miR-591/IRAK3 axis

J Orthop Surg Res. 2021 Mar 3;16(1):170. doi: 10.1186/s13018-021-02323-7.

Abstract

Background: The dysregulation of circular RNAs (circRNAs) has been identified in various human diseases, including osteoarthritis (OA). The purpose of this study was to identify the role and mechanism of circ_SLC39A8 in regulating the progression of OA.

Methods: The expression levels of circ_SLC39A8, miR-591, and its potential target gene, interleukin-1-receptor-associated kinase 3 (IRAK3), were identified by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. The relationship between miR-591 and circ_SLC39A8 or IRAK3 was predicted by bioinformatics tools and verified by dual-luciferase reporter.

Results: Circ_SLC39A8 and IRAK3 were upregulated and miR-591 was downregulated in OA cartilage tissues. Knockdown of circ_SLC39A8 inhibited apoptosis and inflammation in OA chondrocytes, while these effects were reversed by downregulating miR-591. Promotion cell viability effects of miR-591 were partially reversed by IRAK3 overexpression.

Conclusion: Our findings indicated that knockdown of circ_SLC39A8 delayed the progression of OA via modulating the miR-591-IRAK3 axis, providing new insight into the molecular mechanisms of OA pathogenesis.

Keywords: Circ_SLC39A8; IRAK3; Osteoarthritis; miR-591.

MeSH terms

  • Aged
  • Apoptosis / genetics
  • Cation Transport Proteins / genetics*
  • Cation Transport Proteins / physiology*
  • Cell Survival / genetics
  • Cells, Cultured
  • Chondrocytes / metabolism*
  • Chondrocytes / physiology
  • Disease Progression
  • Down-Regulation / genetics
  • Female
  • Gene Knockdown Techniques*
  • Humans
  • Interleukin-1 Receptor-Associated Kinases / genetics
  • Interleukin-1 Receptor-Associated Kinases / metabolism*
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Osteoarthritis / genetics*
  • Osteoarthritis / metabolism

Substances

  • Cation Transport Proteins
  • MIRN591 microRNA, human
  • MicroRNAs
  • SLC39A4 protein, human
  • IRAK3 protein, human
  • Interleukin-1 Receptor-Associated Kinases