Fibroblast growth factor receptor 3 is a negative regulator of bone growth.
Endochondral ossification is a major mode of bone that occurs as chondrocytes undergo proliferation, hypertrophy, cell death, and osteoblastic replacement. We have identified a role for fibroblast growth factor receptor 3 (FGFR-3) in this process by disrupting the murine Fgfr-3 gene to produce severe and progressive bone dysplasia with enhanced and prolonged endochondral bone growth. This growth is accompanied by expansion of proliferating and hypertrophic chondrocytes within the cartilaginous growth plate. Thus, FGFR-3 appears to regulate endochondral ossification by an essentially negative mechanism, limiting rather than promoting osteogenesis. In light of these mouse results, certain human disorders, such as achondroplasia, can be interpreted as gain-of-function mutations that activate the fundamentally negative growth control exerted by the FGFR-3 kinase.
Deng
C
C
Department of Genetics, Harvard Medical School, Boston, Massachusetts, 02115, USA.
Wynshaw-Boris
A
A
Zhou
F
F
Kuo
A
A
Leder
P
P
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001846:Bone Development / Q000235:genetics*; D001842:Bone and Bones / Q000002:abnormalities / Q000166:cytology* / Q000648:ultrastructure; D005346:Fibroblast Growth Factors / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006579:Heterozygote; D017403:In Situ Hybridization; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D010641:Phenotype; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics* / Q000378:metabolism; D013131:Spine / Q000473:pathology; D013234:Stem Cells / Q000502:physiology / Q000648:ultrastructure
D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; C496366:Fgfr3 protein, mouse; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3