Effect of microRNA-145 on IL-1β-induced cartilage degradation in human chondrocytes

FEBS Lett. 2014 Jun 27;588(14):2344-52. doi: 10.1016/j.febslet.2014.05.033. Epub 2014 May 27.

Abstract

MicroRNA-145 has been shown to regulate chondrocyte homeostasis. It seems that miR-145 is implicated in cartilage dysfunction in Osteoarthritis (OA). However, the functional role of miR-145 in interleukin-1 beta (IL-1β)-induced extracellular matrix (ECM) degradation of OA cartilage has never been clarified. Here, we show that miR-145 expression increased in OA chondrocytes and in response to IL-1β stimulation. We confirm that mothers against decapentaplegic homolog 3 (Smad3), a key factor in maintaining chondrocyte homeostasis, is directly regulated by miR-145. Modulation of miR-145 affects the expression of Smad3 causing a change of its downstream target gene expression as well as IL-1β-induced ECM degradation in OA chondrocytes. This indicates that miR-145 contributes to impaired ECM in OA cartilage probably in part via targeting Smad3.

Keywords: Extracellular matrix; Interleukin-1 beta; MicroRNA; MicroRNA-145; Osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aggrecans / metabolism
  • Base Sequence
  • Cartilage / metabolism*
  • Cartilage / pathology
  • Case-Control Studies
  • Cells, Cultured
  • Chondrocytes / metabolism*
  • Collagen Type II / metabolism
  • Humans
  • Interleukin-1beta / physiology*
  • MicroRNAs / physiology*
  • Middle Aged
  • Osteoarthritis, Knee / metabolism
  • RNA Interference
  • Smad3 Protein / metabolism
  • Up-Regulation
  • Young Adult

Substances

  • Aggrecans
  • Collagen Type II
  • Interleukin-1beta
  • MIRN145 microRNA, human
  • MicroRNAs
  • SMAD3 protein, human
  • Smad3 Protein