Related Experiment Video
Updated: Jun 28, 2026

Isolation of Chondrocytes and Chondroprogenitors Using Fibronectin Adhesion and Migratory Assay
Published on: October 4, 2024
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
Abstract:
Activation of fibroblast growth factor receptor 3 (FGFR3) leads to attenuation of cartilage growth. The members of the STAT family of transcription factors are believed to participate in FGFR3 signaling in cartilage, however the molecular mechanism of this action is poorly understood. Here, we demonstrate that a chronic FGF stimulus leads to accumulation of STAT1, 3, 5 and 6, evident in both in vitro chondrocyte model and murine limb explant cultures. Despite the accumulation, both endogenous and cytokine-induced activation of STAT1 and STAT3 is impaired by FGF, as demonstrated by imaging of active STAT nuclear translocation and analyses of STAT activatory phosphorylation and transcriptional activation. Further, we demonstrate that FGF induces expression of CIS, SOCS1 and SOCS3 inhibitors of gp130, a common receptor for the IL6-family of cytokines. Since cytokine-gp130 signaling represents an important positive regulator of cartilage, its inhibition may contribute to the growth-inhibitory effect of FGFR3 in cartilage.
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.
Related Concept Videos
TGF - β Signaling Pathway
The JAK-STAT Signaling Pathway
Introduction to Fibroblasts
Inhibitors of Viral Protein Synthesis
Regulation of Hematopoietic Stem Cells
Role of Hematopoietic Growth Factors
Thrombopoietin (TPO), mainly released by the liver,...