Fibroblast growth factor inhibits interferon gamma-STAT1 and interleukin 6-STAT3 signaling in chondrocytes

Pavel Krejci1, Jirina Prochazkova, Vitezslav Bryja

  • 1Institute of Experimental Biology, Masaryk University, 61137 Brno, Czech Republic. krejcip@sci.muni.cz

Cellular Signalling
|October 28, 2008
PubMed

Insights

Fibroblast growth factor receptor 3 (FGFR3) activation impairs STAT signaling in cartilage. FGF signaling induces STAT inhibitors, potentially explaining FGFR3

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Skeletal Biology

Background:

  • Fibroblast growth factor receptor 3 (FGFR3) activation inhibits cartilage growth.
  • The role of STAT (Signal Transducer and Activator of Transcription) family proteins in FGFR3 signaling within cartilage is not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which FGFR3 signaling affects STAT proteins in cartilage.
  • To investigate the impact of FGF stimulus on STAT accumulation and activation in chondrocytes.

Main Methods:

  • In vitro chondrocyte cultures and murine limb explant models were utilized.
  • Analysis included imaging of STAT nuclear translocation, STAT phosphorylation, and transcriptional activation assays.
  • Gene expression analysis was performed to identify induced inhibitors.

Main Results:

  • Chronic FGF stimulation led to STAT1, STAT3, STAT5, and STAT6 accumulation in chondrocytes and explants.
  • FGF impaired both endogenous and cytokine-induced activation of STAT1 and STAT3.
  • FGF induced the expression of CIS, SOCS1, and SOCS3, which are inhibitors of gp130 signaling.

Conclusions:

  • FGFR3 activation leads to impaired STAT1 and STAT3 activation in cartilage.
  • Induced expression of SOCS and CIS family proteins by FGF may mediate the inhibition of IL6-family cytokine signaling.
  • This inhibition of cytokine-gp130 signaling likely contributes to the growth-attenuating effects of FGFR3 in cartilage.

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