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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2003-8-26
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pubmed:abstractText |
Thyroid hormone (T3) and the T3 receptor (TR) alpha gene are essential for bone development whereas adult hyperthyroidism increases the risk of osteoporotic fracture. We isolated fibroblast growth factor receptor-1 (FGFR1) as a T3-target gene in osteoblasts by subtraction hybridization. FGFR1 mRNA was induced 2- to 3-fold in osteoblasts treated with T3 for 6-48 h, and FGFR1 protein was stimulated 2- to 4-fold. Induction of FGFR1 was independent of mRNA half-life and abolished by actinomycin D and cycloheximide, indicating the involvement of an intermediary protein. Fibroblast growth factor 2 (FGF2) stimulated MAPK in osteoblasts, and pretreatment with T3 for 6 h induced a more rapid response to FGF that was increased in magnitude by 2- to 3-fold. Similarly, T3 enhanced FGF2-activated autophosphorylation of FGFR1, but did not modify FGF2-induced phosphorylation of the docking protein FRS2. These effects were abolished by the FGFR-selective inhibitors PD166866 and PD161570. In situ hybridization analyses of TRalpha-knockout mice, which have impaired ossification and skeletal mineralization, revealed reduced FGFR1 mRNA expression in osteoblasts and osteocytes, whereas T3 failed to stimulate FGFR1 mRNA or enhance FGF2-activated MAPK signaling in TRalpha-null osteoblasts. These findings implicate FGFR1 signaling in T3-dependent bone development and the pathogenesis of skeletal disorders resulting from thyroid disease.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Fgfr1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Fibroblast Growth Factor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/PD 161570,
http://linkedlifedata.com/resource/pubmed/chemical/PD 166866,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Fibroblast Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Fibroblast Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Triiodothyronine,
http://linkedlifedata.com/resource/pubmed/chemical/Urea
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0888-8809
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1751-66
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12805413-Animals,
pubmed-meshheading:12805413-Bone and Bones,
pubmed-meshheading:12805413-Fibroblast Growth Factor 2,
pubmed-meshheading:12805413-Mice,
pubmed-meshheading:12805413-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12805413-Osteoblasts,
pubmed-meshheading:12805413-Phosphorylation,
pubmed-meshheading:12805413-Phosphotransferases,
pubmed-meshheading:12805413-Pyrimidines,
pubmed-meshheading:12805413-Receptor, Fibroblast Growth Factor, Type 1,
pubmed-meshheading:12805413-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:12805413-Receptors, Fibroblast Growth Factor,
pubmed-meshheading:12805413-Signal Transduction,
pubmed-meshheading:12805413-Thyroid Gland,
pubmed-meshheading:12805413-Triiodothyronine,
pubmed-meshheading:12805413-Urea
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pubmed:year |
2003
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pubmed:articleTitle |
Thyroid hormone activates fibroblast growth factor receptor-1 in bone.
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pubmed:affiliation |
Molecular Endocrinology Group, Medical Research Council Clinical Sciences Centre, Clinical Research Building, 5th Floor, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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