Circular RNA VMA21 ameliorates IL-1β-engendered chondrocyte injury through the miR-495-3p/FBWX7 signaling axis

Clin Immunol. 2022 May:238:108995. doi: 10.1016/j.clim.2022.108995. Epub 2022 Apr 1.

Abstract

This study explored the function of circular RNA VMA21 (circVMA21) in osteoarthritis (OA). IL-1β inducement reduced the expression of circVMA21 in C28/I2 cells and human primary chondrocytes. Forced expression of circVMA21 heightened cell viability and attenuated cell apoptosis, accompanied by upregulation of Bcl-2, and downregulation of Bax and C-caspase-3 in C28/I2 cells in response to IL-1β exposure. CircVMA21 overexpression diminished the expression of MMP1 and MMP13, augmented the expression of COL2A1, and impeded the production of IL-6, TNF-α, prostaglandin E2 (PGE2) and NO. CircVMA21 served as a competitive endogenous RNA by sponging miR-495-3p. F-box and WD40 domain protein 7 (FBWX7) was identified as a target of miR-495-3p. The compensation experiments affirmed that circVMA21-mediated protective effects on IL-1β-irritated chondrocytes through the miR-495-3p/FBWX7 axis. The role of circVMA21 was also confirmed in an OA rat model. Collectively, these findings revealed a protective effect of circVMA21in OA by intercepting the miR-495-3p/FBWX7 crosstalk.

Keywords: Apoptosis; Extracellular matrix; FBWX7; Osteoarthritis; circVMA21; miR-495-3p.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Chondrocytes* / drug effects
  • Chondrocytes* / metabolism
  • F-Box Proteins
  • Humans
  • Interleukin-1beta / pharmacology
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Osteoarthritis* / genetics
  • Osteoarthritis* / metabolism
  • RNA, Circular* / genetics
  • Rats
  • Signal Transduction

Substances

  • F-Box Proteins
  • FBXO41 protein, human
  • Interleukin-1beta
  • MIRN495 microRNA, human
  • MicroRNAs
  • RNA, Circular