| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on April 15, 2003
Accepted on May 29, 2003
1 Molecular Endocrinology Group, Division of Medicine & MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK; Epistem Ltd. and School of Biological Sciences, University of Manchester, Oxford Road, Manchester, UK; Laboratoire de Biologie Moléculaire et Cellulaire de l'ENS de Lyon, UMR 5665 CNRS, LA 913 INRA, Lyon, France; Unité INSERM U-443, Université Victor Segalen Bordeaux 2, Bordeaux, France
* To whom correspondence should be addressed. E-mail: graham.williams{at}ic.ac.uk.
Thyroid hormone (T3) and the T3 receptor (TR) 
gene are essential for bone development whilst 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 2-3 fold in osteoblasts treated with T3 for 6-48 h and FGFR1 protein was stimulated 2-4 fold. Induction of FGFR1 was independent of mRNA half-life and abolished by actinomycin D and cycloheximide, indicating the involvement of an intermediary protein. FGF2 stimulated mitogen-activated protein kinase (MAPK) in osteoblasts and pre-treatment with T3 for 6 h induced a more rapid response to FGF that was increased in magnitude by 2-3 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 TR-knockout mice, which have impaired ossification and skeletal mineralization, revealed reduced FGFR1 mRNA expression in osteoblasts and osteocytes, whilst T3 failed to stimulate FGFR1 mRNA or enhance FGF2-activated MAPK signaling in TR-null osteoblasts. These findings implicate FGFR1 signaling in T3-dependent bone development and the pathogenesis of skeletal disorders resulting from thyroid disease.
NURSA Molecule Pages Link:
This article has been cited by other articles:
 |
|
 |
|
  A Scarlett, M P Parsons, P L Hanson, K K Sidhu, T P Milligan, and J M Burrin Thyroid hormone stimulation of extracellular signal-regulated kinase and cell proliferation in human osteoblast-like cells is initiated at integrin {alpha}V{beta}3 J. Endocrinol., March 1, 2008; 196(3): 509 - 517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. D. Bassett, A. J. Williams, E. Murphy, A. Boyde, P. G. T. Howell, R. Swinhoe, M. Archanco, F. Flamant, J. Samarut, S. Costagliola, et al. A Lack of Thyroid Hormones Rather than Excess Thyrotropin Causes Abnormal Skeletal Development in Hypothyroidism Mol. Endocrinol., February 1, 2008; 22(2): 501 - 512. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. O'Shea, C. J. Guigon, G. R. Williams, and S.-y. Cheng Regulation of Fibroblast Growth Factor Receptor-1 (Fgfr1) by Thyroid Hormone: Identification of a Thyroid Hormone Response Element in the Murine Fgfr1 Promoter Endocrinology, December 1, 2007; 148(12): 5966 - 5976. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. D. Bassett, K. Nordstrom, A. Boyde, P. G. T. Howell, S. Kelly, B. Vennstrom, and G. R. Williams Thyroid Status during Skeletal Development Determines Adult Bone Structure and Mineralization Mol. Endocrinol., August 1, 2007; 21(8): 1893 - 1904. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. D. Bassett, P. J. O'Shea, S. Sriskantharajah, B. Rabier, A. Boyde, P. G. T. Howell, R. E. Weiss, J.-P. Roux, L. Malaval, P. Clement-Lacroix, et al. Thyroid Hormone Excess Rather Than Thyrotropin Deficiency Induces Osteoporosis in Hyperthyroidism Mol. Endocrinol., May 1, 2007; 21(5): 1095 - 1107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Rabier, A. J Williams, F. Mallein-Gerin, G. R Williams, and O Chassande Thyroid hormone-stimulated differentiation of primary rib chondrocytes in vitro requires thyroid hormone receptor {beta}. J. Endocrinol., October 1, 2006; 191(1): 221 - 228. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Mousa, L. O'Connor, F. B. Davis, and P. J. Davis Proangiogenesis Action of the Thyroid Hormone Analog 3,5-Diiodothyropropionic Acid (DITPA) Is Initiated at the Cell Surface and Is Integrin Mediated Endocrinology, April 1, 2006; 147(4): 1602 - 1607. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. O'Shea, J. H. D. Bassett, S. Sriskantharajah, H. Ying, S.-y. Cheng, and G. R. Williams Contrasting Skeletal Phenotypes in Mice with an Identical Mutation Targeted to Thyroid Hormone Receptor {alpha}1 or {beta} Mol. Endocrinol., December 1, 2005; 19(12): 3045 - 3059. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Barnard, A. J. Williams, B. Rabier, O. Chassande, J. Samarut, S.-y. Cheng, J. H. D. Bassett, and G. R. Williams Thyroid Hormones Regulate Fibroblast Growth Factor Receptor Signaling during Chondrogenesis Endocrinology, December 1, 2005; 146(12): 5568 - 5580. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
