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Developmental Biology
Article
License: Elsevier Non-Commercial
Data sources: UnpayWall
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Developmental Biology
Article . 2007
License: Elsevier Non-Commercial
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Developmental Biology
Article . 2007 . Peer-reviewed
License: Elsevier Non-Commercial
Data sources: Crossref
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FGF18 is required for early chondrocyte proliferation, hypertrophy and vascular invasion of the growth plate

Authors: David M. Ornitz; Zhonghao Liu; Kory J. Lavine; Irene H. Hung;

FGF18 is required for early chondrocyte proliferation, hypertrophy and vascular invasion of the growth plate

Abstract

Fibroblast growth factor 18 (FGF18) has been shown to regulate chondrocyte proliferation and differentiation by signaling through FGF receptor 3 (FGFR3) and to regulate osteogenesis by signaling through other FGFRs. Fgf18(-/-) mice have an apparent delay in skeletal mineralization that is not seen in Fgfr3(-/-) mice. However, this delay in mineralization could not be simply explained by FGF18 signaling to osteoblasts. Here we show that delayed mineralization in Fgf18(-/-) mice was closely associated with delayed initiation of chondrocyte hypertrophy, decreased proliferation at early stages of chondrogenesis, delayed skeletal vascularization and delayed osteoclast and osteoblast recruitment to the growth plate. We further show that FGF18 is necessary for Vegf expression in hypertrophic chondrocytes and the perichondrium and is sufficient to induce Vegf expression in skeletal explants. These findings support a model in which FGF18 regulates skeletal vascularization and subsequent recruitment of osteoblasts/osteoclasts through regulation of early stages of chondrogenesis and VEGF expression. FGF18 thus coordinates neovascularization of the growth plate with chondrocyte and osteoblast growth and differentiation.

Keywords

Vascular Endothelial Growth Factor A, Fibroblast growth factor 18 (FGF18), Skeletal development, Neovascularization, Physiologic, Osteoclasts, In Vitro Techniques, Mice, Chondrocytes, Perichondrium, Osteogenesis, Periosteum, Animals, Growth Plate, Molecular Biology, Cell Proliferation, Osteoblasts, Osteoblast, Gene Expression Regulation, Developmental, Vascular development, Extremities, Cell Biology, Chondrocyte, Embryo, Mammalian, Fibroblast Growth Factors, Receptors, Vascular Endothelial Growth Factor, Lac Operon, Growth plate, Chondrogenesis, Developmental Biology

  • BIP!
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    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    180
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 1%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
Powered by OpenAIRE graph
citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
180
Top 1%
Top 10%
Top 1%
hybrid