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Coordination of chondrogenesis and osteogenesis by fibroblast growth factor 18.
Genes Dev. 2002 Apr 01; 16(7):859-69.GD

Abstract

Gain of function mutations in fibroblast growth factor (FGF) receptors cause chondrodysplasia and craniosynostosis syndromes. The ligands interacting with FGF receptors (FGFRs) in developing bone have remained elusive, and the mechanisms by which FGF signaling regulates endochondral, periosteal, and intramembranous bone growth are not known. Here we show that Fgf18 is expressed in the perichondrium and that mice homozygous for a targeted disruption of Fgf18 exhibit a growth plate phenotype similar to that observed in mice lacking Fgfr3 and an ossification defect at sites that express Fgfr2. Mice lacking either Fgf18 or Fgfr3 exhibited expanded zones of proliferating and hypertrophic chondrocytes and increased chondrocyte proliferation, differentiation, and Indian hedgehog signaling. These data suggest that FGF18 acts as a physiological ligand for FGFR3. In addition, mice lacking Fgf18 display delayed ossification and decreased expression of osteogenic markers, phenotypes not seen in mice lacking Fgfr3. These data demonstrate that FGF18 signals through another FGFR to regulate osteoblast growth. Signaling to multiple FGFRs positions FGF18 to coordinate chondrogenesis in the growth plate with osteogenesis in cortical and trabecular bone.

Authors+Show Affiliations

Department of Molecular Biology and Pharmacology, Washington University Medical School, St. Louis, Missouri 63110, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11937493

Citation

Liu, Zhonghao, et al. "Coordination of Chondrogenesis and Osteogenesis By Fibroblast Growth Factor 18." Genes & Development, vol. 16, no. 7, 2002, pp. 859-69.
Liu Z, Xu J, Colvin JS, et al. Coordination of chondrogenesis and osteogenesis by fibroblast growth factor 18. Genes Dev. 2002;16(7):859-69.
Liu, Z., Xu, J., Colvin, J. S., & Ornitz, D. M. (2002). Coordination of chondrogenesis and osteogenesis by fibroblast growth factor 18. Genes & Development, 16(7), 859-69.
Liu Z, et al. Coordination of Chondrogenesis and Osteogenesis By Fibroblast Growth Factor 18. Genes Dev. 2002 Apr 1;16(7):859-69. PubMed PMID: 11937493.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Coordination of chondrogenesis and osteogenesis by fibroblast growth factor 18. AU - Liu,Zhonghao, AU - Xu,Jingsong, AU - Colvin,Jennifer S, AU - Ornitz,David M, PY - 2002/4/9/pubmed PY - 2002/5/15/medline PY - 2002/4/9/entrez SP - 859 EP - 69 JF - Genes & development JO - Genes Dev. VL - 16 IS - 7 N2 - Gain of function mutations in fibroblast growth factor (FGF) receptors cause chondrodysplasia and craniosynostosis syndromes. The ligands interacting with FGF receptors (FGFRs) in developing bone have remained elusive, and the mechanisms by which FGF signaling regulates endochondral, periosteal, and intramembranous bone growth are not known. Here we show that Fgf18 is expressed in the perichondrium and that mice homozygous for a targeted disruption of Fgf18 exhibit a growth plate phenotype similar to that observed in mice lacking Fgfr3 and an ossification defect at sites that express Fgfr2. Mice lacking either Fgf18 or Fgfr3 exhibited expanded zones of proliferating and hypertrophic chondrocytes and increased chondrocyte proliferation, differentiation, and Indian hedgehog signaling. These data suggest that FGF18 acts as a physiological ligand for FGFR3. In addition, mice lacking Fgf18 display delayed ossification and decreased expression of osteogenic markers, phenotypes not seen in mice lacking Fgfr3. These data demonstrate that FGF18 signals through another FGFR to regulate osteoblast growth. Signaling to multiple FGFRs positions FGF18 to coordinate chondrogenesis in the growth plate with osteogenesis in cortical and trabecular bone. SN - 0890-9369 UR - https://www.unboundmedicine.com/medline/citation/11937493/Coordination_of_chondrogenesis_and_osteogenesis_by_fibroblast_growth_factor_18_ L2 - http://www.genesdev.org/cgi/pmidlookup?view=long&pmid=11937493 DB - PRIME DP - Unbound Medicine ER -