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Updated: May 6, 2026

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Fibroblast growth factor receptor 3 is a negative regulator of bone growth

C Deng1, A Wynshaw-Boris, F Zhou

  • 1Department of Genetics, Harvard Medical School, Boston, Massachusetts, 02115, USA.

Cell
|March 22, 1996
PubMed

Insights

Fibroblast growth factor receptor 3 (FGFR-3) negatively regulates endochondral ossification, a key bone development process. Disrupting the Fgfr-3 gene in mice led to enhanced bone growth, suggesting FGFR-3 limits bone formation.

Area of Science:

  • Skeletal Biology
  • Developmental Biology
  • Molecular Genetics

Background:

  • Endochondral ossification is crucial for bone formation, involving chondrocyte proliferation, hypertrophy, death, and replacement by osteoblasts.
  • Fibroblast growth factor receptor 3 (FGFR-3) is implicated in skeletal development, but its precise role in endochondral ossification requires further elucidation.

Purpose of the Study:

  • To investigate the role of fibroblast growth factor receptor 3 (FGFR-3) in the process of endochondral ossification.
  • To determine the effects of FGFR-3 disruption on bone growth and chondrocyte dynamics within the growth plate.

Main Methods:

  • Gene disruption of the murine Fgfr-3 gene.
  • Analysis of skeletal phenotypes, including bone dysplasia and growth plate morphology.
  • Evaluation of chondrocyte proliferation and hypertrophy.

Main Results:

  • Disruption of the Fgfr-3 gene resulted in severe and progressive bone dysplasia in mice.
  • FGFR-3 deficient mice exhibited enhanced and prolonged endochondral bone growth.
  • An expansion of proliferating and hypertrophic chondrocytes was observed in the cartilaginous growth plate.

Conclusions:

  • Fibroblast growth factor receptor 3 (FGFR-3) acts as a negative regulator of endochondral ossification, limiting osteogenesis.
  • FGFR-3 signaling restricts chondrocyte proliferation and hypertrophy within the growth plate.
  • Human disorders like achondroplasia may result from gain-of-function mutations in FGFR-3, leading to excessive negative growth control.

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