About: FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway

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About: FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway Goto Sponge NotDistinct Permalink

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
Description	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. 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. (en)
Title	FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway (en)
skos:prefLabel	FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway (en)
skos:notation	RIV/00216224:14310/09:00039941!RIV10-MSM-14310___
http://linked.open...avai/riv/aktivita	S Z
http://linked.open...avai/riv/aktivity	S, Z(AV0Z50040507), Z(AV0Z50040702)
http://linked.open...iv/cisloPeriodika	2
http://linked.open...vai/riv/dodaniDat	2010
http://linked.open...aciTvurceVysledku	Krejčí, Pavel
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Masarykova univerzita / Přírodovědecká fakulta
http://linked.open...dnocenehoVysledku	314890
http://linked.open...ai/riv/idVysledku	RIV/00216224:14310/09:00039941
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	FIBROBLAST-GROWTH-FACTOR; FACTOR RECEPTOR-3; TRANSGENIC MICE; CRE RECOMBINASE; BONE-FORMATION; CHONDROCYTE PROLIFERATION; THANATOPHORIC DYSPLASIA; TARGETED DISRUPTION; ACHONDROPLASIA; EXPRESSION (en)
http://linked.open.../riv/klicoveSlovo	BONE-FORMATION CHONDROCYTE PROLIFERATION CRE RECOMBINASE FACTOR RECEPTOR-3 TARGETED DISRUPTION TRANSGENIC MICE EXPRESSION THANATOPHORIC DYSPLASIA ACHONDROPLASIA FIBROBLAST-GROWTH-FACTOR
http://linked.open...odStatuVydavatele	US - Spojené státy americké
http://linked.open...ontrolniKodProRIV	[5FF71527B0E5]
http://linked.open...i/riv/nazevZdroje	Human Molecular Genetics
http://linked.open...in/vavai/riv/obor	EB
http://linked.open...ichTvurcuVysledku	1 (xsd:int)
http://linked.open...cetTvurcuVysledku	13 (xsd:int)
http://linked.open...UplatneniVysledku	2009
http://linked.open...v/svazekPeriodika	18
http://linked.open...iv/tvurceVysledku	Krejčí, Pavel Murakami, Shunichi Wilcox, William Balmes, Gener Bükülmez, Hülya Givol, David Kawanami, Aya Matsushita, Takehiko Mekikian, Pertchoui B Otani, Kazuyuki Warman, Matthew L. Yamaura, Isakichi Yuk Yu, Chan
http://linked.open...ain/vavai/riv/wos	000261897500002
http://linked.open...n/vavai/riv/zamer	Biophysics of dynamic structures and functions of biological systems Genome and epigenome: 1D and 3D Structure, Dynamics, Interactions with Proteins and Functions
issn	0964-6906
number of pages	240 (xsd:int)
http://localhost/t...ganizacniJednotka	14310

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