Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Apr 29;2:14003.
doi: 10.1038/boneres.2014.3. eCollection 2014.

Role of FGF/FGFR Signaling in Skeletal Development and Homeostasis: Learning From Mouse Models

Affiliations
Free PMC article
Review

Role of FGF/FGFR Signaling in Skeletal Development and Homeostasis: Learning From Mouse Models

Nan Su et al. Bone Res. .
Free PMC article

Abstract

Fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) signaling plays essential roles in bone development and diseases. Missense mutations in FGFs and FGFRs in humans can cause various congenital bone diseases, including chondrodysplasia syndromes, craniosynostosis syndromes and syndromes with dysregulated phosphate metabolism. FGF/FGFR signaling is also an important pathway involved in the maintenance of adult bone homeostasis. Multiple kinds of mouse models, mimicking human skeleton diseases caused by missense mutations in FGFs and FGFRs, have been established by knock-in/out and transgenic technologies. These genetically modified mice provide good models for studying the role of FGF/FGFR signaling in skeleton development and homeostasis. In this review, we summarize the mouse models of FGF signaling-related skeleton diseases and recent progresses regarding the molecular mechanisms, underlying the role of FGFs/FGFRs in the regulation of bone development and homeostasis. This review also provides a perspective view on future works to explore the roles of FGF signaling in skeletal development and homeostasis.

Figures

Figure 1
Figure 1
Signaling pathways activated by FGF/FGFR. FGFs induce dimerization, kinase activation and transphosphorylation of tyrosine residues of FGFRs, leading to activation of downstream signaling pathways. Multiple pathways are stimulated by FGF/FGFR signaling such as Ras-MAP kinase, PI-3 kinase/AKT and PLC-γ pathways. Furthermore, FGF signaling can also stimulate STAT1/p21 pathway. FGF/FGFR signaling also phosphorylates the Shc and Src protein. FGF/FGFR play crucial roles in the regulation of proliferation, differentiation and apoptosis of chondrocytes via downstream signaling pathways.
Figure 2
Figure 2
The regulation of osteogenesis by FGFR1-3. FGFRs play distinct roles during the differentiation of osteoblast. There are some conflicting results about the effect of FGFR3 on osteogenesis, which is marked by dotted lines.
Figure 3
Figure 3
FGF23 regulates systemic phosphate homeostasis and vitamin D metabolism. FGF23 can reduce expression of NaPi-2a in kidney tubules and lead to renal phosphate wasting. FGF23 downregulates activity of 25-hydroxyvitamin D 1a-hydroxylase in kidney tubules and reduces 1,25(OH)2D level. Furthermore, FGF23 also have relationship with PTH and PHEX.

Similar articles

See all similar articles

Cited by 59 articles

See all "Cited by" articles

References

    1. Karsenty G, Wagner EF. Reaching a genetic and molecular understanding of skeletal development. Dev Cell. 2002;2:389–406. - PubMed
    1. Su N, Du X, Chen L. FGF signaling: its role in bone development and human skeleton diseases. Front Biosci. 2008;13:2842–2865. - PubMed
    1. Chen L, Deng CX. Roles of FGF signaling in skeletal development and human genetic diseases. Front Biosci. 2005;10:1961–1976. - PubMed
    1. Johnson DE, Williams LT. Structural and functional diversity in the FGF receptor multigene family. Adv Cancer Res. 1993;60:1–41. - PubMed
    1. Ornitz DM, Xu J, Colvin JS. Receptor specificity of the fibroblast growth factor family. J Biol Chem. 1996;271:15292–15297. - PubMed

LinkOut - more resources

Feedback