| MATSUSHITA, Takehiko, William WILCOX, Chan YUK YU, Aya KAWANAMI, Hülya BÜKÜLMEZ, Gener BALMES, Pavel KREJČÍ, Pertchoui B MEKIKIAN, Kazuyuki OTANI, Isakichi YAMAURA, Matthew L. WARMAN, David GIVOL a Shunichi MURAKAMI. FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway. Human Molecular Genetics. 2009, roč. 18, č. 2, 227-240. ISSN 0964-6906. |
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@article{879423,
author = {Matsushita, Takehiko and Wilcox, William and Yuk Yu, Chan and Kawanami, Aya and Bükülmez, Hülya and Balmes, Gener and Krejčí, Pavel and Mekikian, Pertchoui B and Otani, Kazuyuki and Yamaura, Isakichi and Warman, Matthew L. and Givol, David and Murakami, Shunichi},
article_number = {2},
keywords = {FIBROBLAST-GROWTH-FACTOR; FACTOR RECEPTOR-3; TRANSGENIC MICE; CRE RECOMBINASE; BONE-FORMATION; CHONDROCYTE PROLIFERATION; THANATOPHORIC DYSPLASIA; TARGETED DISRUPTION; ACHONDROPLASIA; EXPRESSION},
language = {eng},
issn = {0964-6906},
journal = {Human Molecular Genetics},
title = {FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway},
volume = {18},
year = {2009}
}
TY - JOUR
ID - 879423
AU - Matsushita, Takehiko - Wilcox, William - Yuk Yu, Chan - Kawanami, Aya - Bükülmez, Hülya - Balmes, Gener - Krejčí, Pavel - Mekikian, Pertchoui B - Otani, Kazuyuki - Yamaura, Isakichi - Warman, Matthew L. - Givol, David - Murakami, Shunichi
PY - 2009
TI - FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway
JF - Human Molecular Genetics
VL - 18
IS - 2
SN - 09646906
KW - FIBROBLAST-GROWTH-FACTOR
KW - FACTOR RECEPTOR-3
KW - TRANSGENIC MICE
KW - CRE RECOMBINASE
KW - BONE-FORMATION
KW - CHONDROCYTE PROLIFERATION
KW - THANATOPHORIC DYSPLASIA
KW - TARGETED DISRUPTION
KW - ACHONDROPLASIA
KW - EXPRESSION
N2 - Activating mutations in FGFR3 cause achondroplasia and thanatophoric dysplasia, the most common human skeletal dysplasias. In these disorders, spinal canal and foramen magnum stenosis can cause serious neurologic complications. Here, we provide evidence that FGFR3 and MAPK signaling in chondrocytes promote synchondrosis closure and fusion of ossification centers. We observed premature synchondrosis closure in the spine and cranial base in human cases of homozygous achondroplasia and thanatophoric dysplasia as well as in mouse models of achondroplasia. In both species, premature synchondrosis closure was associated with increased bone formation. Chondrocyte-specific activation of Fgfr3 in mice induced premature synchondrosis closure and enhanced osteoblast differentiation around synchondroses. FGF signaling in chondrocytes increases Bmp ligand mRNA expression and decreases Bmp antagonist mRNA expression in a MAPK-dependent manner, suggesting a role for Bmp signaling in the increased bone formation. The enhanced bone formation would accelerate the fusion of ossification centers and limit the endochondral bone growth. Spinal canal and foramen magnum stenosis in heterozygous achondroplasia patients, therefore, may occur through premature synchondrosis closure. If this is the case, then any growth-promoting treatment for these complications of achondroplasia must precede the timing of the synchondrosis closure.
ER -
MATSUSHITA, Takehiko, William WILCOX, Chan YUK YU, Aya KAWANAMI, Hülya BÜKÜLMEZ, Gener BALMES, Pavel KREJČÍ, Pertchoui B MEKIKIAN, Kazuyuki OTANI, Isakichi YAMAURA, Matthew L. WARMAN, David GIVOL a Shunichi MURAKAMI. FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway. \textit{Human Molecular Genetics}. 2009, roč.~18, č.~2, 227-240. ISSN~0964-6906.
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