miR9 inhibits 6-mer HA-induced cytokine production and apoptosis in human chondrocytes by reducing NF-kB activation

Arch Biochem Biophys. 2022 Mar 30:718:109139. doi: 10.1016/j.abb.2022.109139. Epub 2022 Feb 1.

Abstract

The present study aimed to investigate the expression of miR9 and its correlation with cytokines, proteolytic enzymes and apoptosis in an experimental model of 6-mer HA induced inflammation in human chondrocytes. Human articular chondrocytes, transfected with a miR-9 mimic and miR-9 inhibitor, were stimulated with 6-mer HA in presence/absence of a specific NF-kB inhibitor. 6-mer HA induced a significant increase of TLR-4, CD44, IL-8, IL-18, MMP-9, ADAMTS-5, BAX and BCL-2 mRNAs expression and the related proteins, as well as NF-kB activation, associated with a significant up regulation of miR-9. In chondrocytes transfected with the miR-9 mimic before 6-mer HA treatment we found a decrease of such inflammatory cytokines, metalloproteases and pro-apoptotic molecules, while we found them increased in chondrocytes transfected with the miR9 inhibitor before 6-mer HA stimulation. The activities of TLR-4 and CD44, up regulated by 6-mer HA, were not modified by miR9 mimic/inhibitor, while the NF-kB activation was significantly affected. We suggested that the up regulation of miR9, induced by 6-mer HA, could be a cellular attempt to limit cell damage during inflammation.

Keywords: Chondrocytes; Cytokines; Hyaluronan; Inflammation; Metalloproteases; TLRs; miRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cells, Cultured
  • Chondrocytes* / metabolism
  • Cytokines / metabolism
  • Humans
  • Hyaluronic Acid / metabolism
  • Inflammation / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • NF-kappa B / metabolism
  • Toll-Like Receptor 4 / metabolism

Substances

  • Cytokines
  • MIRN92 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • Toll-Like Receptor 4
  • Hyaluronic Acid