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Updated: Mar 6, 2026

Isolation of Chondrocytes and Chondroprogenitors Using Fibronectin Adhesion and Migratory Assay
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Phosphoproteomics of Fibroblast Growth Factor 1 (FGF1) Signaling in Chondrocytes: Identifying the Signature of

Jessica R Chapman1, Olga Katsara2, Rachel Ruoff2

  • 1From the ‡Proteomics Laboratory.

Molecular & Cellular Proteomics : MCP
|March 17, 2017
PubMed

Insights

Fibroblast growth factor (FGF) signaling inhibits chondrocyte growth. This study identifies key proteins, including GSK3β, mediating this unique FGF inhibitory response in bone development.

Area of Science:

  • Skeletal Biology
  • Cell Signaling
  • Molecular Medicine

Background:

  • Fibroblast growth factor (FGF) signaling is crucial for development and skeleton formation.
  • FGFR mutations cause bone disorders like achondroplasia, highlighting FGF's role in chondrocyte function.
  • Chondrocytes exhibit a unique FGF-induced growth inhibition, unlike other cell types, with unclear molecular mechanisms.

Purpose of the Study:

  • To comprehensively identify proteins regulated by FGF1 in chondrocytes.
  • To elucidate the molecular determinants of FGF-induced growth inhibition in chondrocytes.
  • To define the divergence point between canonical and chondrocyte-specific FGF signaling pathways.

Main Methods:

  • Quantitative phosphoproteomics was employed to analyze protein phosphorylation changes after FGF1 treatment.
  • Gene Ontology (GO) analysis was used to categorize the functions of identified phosphoproteins.
  • Specific signaling mediators were investigated for their role in the FGF inhibitory response.

Main Results:

  • A dataset of 756 proteins with altered phosphorylation status upon FGF1 treatment was generated.
  • The divergence between proliferative and inhibitory FGF signaling pathways was localized upstream of AKT kinase.
  • Phosphorylated proteins were enriched in negative regulation pathways, consistent with growth inhibition.

Conclusions:

  • This study provides the first comprehensive catalog of proteins involved in the FGF inhibitory response in chondrocytes.
  • Glycogen synthase kinase3β (GSK3β) was identified as a novel key mediator of FGF-induced growth inhibition in chondrocytes.
  • Understanding these pathways is vital for addressing skeletal morphogenetic disorders.

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