Fibroblast Growth Factor Receptor (FGFR) and Bone: Implications for Human Growth

  • Richard G. Boles
  • Valairat Dhamcharee


The fibroblast growth factors (FGFs) constitute a family of 22 structurally related polypeptides with diverse biological functions. Their expression is controlled at the levels of transcription, mRNA stability, and translation. Signal transduction occurs when FGFs interact with a family of seven fibroblast growth factors receptors (FGFRs) and cell-surface-associated heparan sulfate proteoglycans. FGFs and FGFRs are key players in the processes of proliferation and differentiation of a wide variety of cells and tissues, including roles in chondrogenesis, osteogenesis, angiogenesis, and wound healing. In osteogenesis, the FGF/FGFR system promotes proliferation, maturation, and differentiation of osteoblasts, as well as bone matrix mineralization. Known human mutations in the FGFR genes result in a gain of function and are broadly classified into two groups: craniosynostosis and chondrodysplasia. Craniosynostosis, or premature closure of one or more sutures of the skull, can occur alone or as part of a syndrome, associated with bony malformations of the face, hands, and/or feet. Paradoxically, the shortened bones of chondrodysplasia can result from receptor activation that inhibits chondrocyte cell growth through cell-type specific signaling pathways. Clinical manifestations range from mild short stature to extremely short limbs with lethal thoracic dysplasia, with the common dwarfism syndrome of achondroplasia located in the middle of this range. FGF23 plays critical roles in phosphate and vitamin D metabolism, and mutation results in the severely depleted bone mineralization of hypophosphatemia. Future advances in bone regeneration may result from a better understanding of the FGF/FGFR system.


Fibroblast Growth Factor Receptor Acanthosis Nigricans Hypophosphatemic Rickets Apical Ectodermal Ridge Kallmann Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.





Autosomal dominant hypophosphatemic rickets


Apical ectodermal ridge


Bone morphogenetic protein


Cell adhesion molecule


Carboxymethyl benzylamide sulfonate


Extracellular signal-related kinases 1/2


Fibroblast growth factor


Fibroblast growth factor receptor


Fibroblast growth factor homologous factor


FGF receptor substrate 2 protein


Growth factor receptor-bound protein 2




Heparan sulfate proteoglycan


Insulin-like growth factor


Kallmann syndrome


Mitogen-activated protein kinase


Sodium phosphate transporters






Platelets derived growth factor


Phosphatidylinositol 3 kinase


Protein kinase C


Parathyroid hormone


Progress zone


Runt-related transcription factor 2


Stress-activated protein kinase/c-Jun N-terminal kinase


Son of sevenless protein


Thanatophoric dysplasia


Transforming growth factor


Transforming growth factor-β


Vascular endothelial growth factor


Combination of Wg (wingless) and Int gene


Zone of polarizing activity


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Division of Medical GeneticsSaban Research Institute, Childrens Hospital Los AngelesLos AngelesUSA
  2. 2.Department of PediatricsKeck School of Medicine, Childrens Hospital Los Angeles, University of Southern CaliforniaLos AngelesUSA
  3. 3.USC Division of Neonatal Medicine, Department of PediatricsKeck School of Medicine, Childrens Hospital Los Angeles, University of Southern CaliforniaLos AngelesUSA

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