MiR-193b regulates early chondrogenesis by inhibiting the TGF-beta2 signaling pathway

FEBS Lett. 2015 Apr 13;589(9):1040-7. doi: 10.1016/j.febslet.2015.02.017. Epub 2015 Feb 26.

Abstract

Cartilage generation and degradation are regulated by miRNAs. Our previous study has shown altered expression of miR-193b in chondrogenic human adipose-derived mesenchymal stem cells (hADSCs). In the current study, we investigated the role of miR-193b in chondrogenesis and cartilage degradation. Luciferase reporter assays showed that miR-193b targeted seed sequences of the TGFB2 and TGFBR3 3'-UTRs. MiR-193b suppressed the expression of early chondrogenic markers in chondrogenic ATDC5 cells, and TNF-alpha expression in IL-1b-induced PMCs. In conclusion, MiR-193b may inhibit early chondrogenesis by targeting TGFB2 and TGFBR3, and may regulate inflammation by repressing TNF-alpha expression in inflamed chondrocytes.

Keywords: Chondrogenesis; MiR-193b; Osteoarthritis; TGF-beta; TNF-alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adipose Tissue / cytology
  • Animals
  • Blotting, Western
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cells, Cultured
  • Chondrocytes / cytology
  • Chondrocytes / metabolism
  • Chondrogenesis / genetics*
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Gene Expression
  • Humans
  • Interleukin-1beta / pharmacology
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • MicroRNAs / genetics*
  • Phosphorylation
  • Proteoglycans / genetics*
  • Proteoglycans / metabolism
  • RNA Interference
  • Receptors, Transforming Growth Factor beta / genetics*
  • Receptors, Transforming Growth Factor beta / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • SOX9 Transcription Factor / genetics
  • SOX9 Transcription Factor / metabolism
  • Signal Transduction / genetics*
  • Smad3 Protein / genetics
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta2 / genetics*
  • Transforming Growth Factor beta2 / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • 3' Untranslated Regions
  • Core Binding Factor Alpha 1 Subunit
  • Interleukin-1beta
  • MIRN193 microRNA, human
  • MicroRNAs
  • Proteoglycans
  • Receptors, Transforming Growth Factor beta
  • SOX9 Transcription Factor
  • Smad3 Protein
  • Transforming Growth Factor beta2
  • Tumor Necrosis Factor-alpha
  • betaglycan