Regulation of Fibroblast Growth Factor Receptor-1 (Fgfr1) by Thyroid Hormone: Identification of a Thyroid Hormone Response Element in the Murine Fgfr1 Promoter
Abstract
T3 is essential for normal skeletal development, acting mainly via the TRα1 nuclear receptor. Nevertheless, the mechanisms of T3 action in bone are poorly defined. Fibroblast growth factor receptor-1 (FGFR1) is also essential for bone formation. Fgfr1 expression and activity are positively regulated by T3 in osteoblasts, and in mice that harbor a dominant negative PV mutation targeted to TRα1 or TRβ, Fgfr1 expression is sensitive to skeletal thyroid status. To investigate mechanisms underlying T3 regulation of FGFR1, we obtained primary calvarial osteoblasts from wild-type and TRβPV/PV littermate mice. T3 treatment increased Fgfr1 expression 2-fold in wild-type cells, but 8-fold in TRβPV/PV osteoblasts. The 4-fold increased T3 sensitivity of TRβPV/PV osteoblasts was associated with a markedly increased ratio of TRα1:TRβ1 expression that resulted from reduced TRβ1 expression in TRβPV/PV osteoblasts compared with wild-type. Bioinformatics and gel shift studies, and mutational analysis, identified a specific TR binding site 279–264 nucleotides upstream of the murine Fgfr1 promoter transcription start site. Transient transfection analysis of a series of Fgfr1 promoter 5′-deletion constructs, of a mutant reporter construct, and a series of heterologous promoter constructs, confirmed that this region of the promoter mediates a TR-dependent transcriptional response to T3. Thus, in addition to indirect regulation of FGFR1 expression by T3 reported previously, T3 also activates the Fgfr1 promoter directly via a thyroid hormone response element located at positions −279/−264.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Thyroid hormone T3 modulates FGFR1 signaling.
“Although the thyroid hormone T3 modulates FGFR1 signaling [18,19,20], no explicit genotype-phenotype correlation links this variant to thyroid dysfunction.”
From Strengthening the Role of PSMC5 as a Potential Gene Associated with Neurodevelopmental Disorders (2025) · cites this paper as [20]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Physiological and Molecular Basis of Thyroid Hormone Action
Yen, P. M. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.3.1097 · Cited by 2,011 · see citing works
Coregulator Function: A Key to Understanding Tissue Specificity of Selective Receptor Modulators
Smith, C. L., & O’Malley, B. W. (2004) · Endocrine Reviews · doi:10.1210/er.2003-0023 · Cited by 931 · see citing works
Ornitz, D. M., & Marie, P. J. (2002) · Genes & Development · doi:10.1101/gad.990702 · Cited by 902 · see citing works
Grant, S. F. A., Reid, D. M., Blake, G., Herd, R., Fogelman, I., & Ralston, S. H. (1996) · Nature Genetics · doi:10.1038/ng1096-203 · Cited by 625 · see citing works
Hoey, T., Weinzierl, R., Gill, G., Chen, J.-L., Dynlacht, B., & Tjian, R. (1993) · Cell · doi:10.1016/0092-8674(93)90664-c · Cited by 533 · see citing works
Mechanisms of thyroid hormone receptor-specific nuclear and extra nuclear actions
Bassett, J. H. D., Harvey, C. B., & Williams, G. R. (2003) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2003.10.033 · Cited by 392 · see citing works
Self-citationChen, J., Attardi, L. D., Verrijzer, C. P., Yokomori, K., & Tjian, R. (1994) · Cell · doi:10.1016/0092-8674(94)90403-0 · Cited by 370 · see citing works
Baniahmad, A., Ha, I., Reinberg, D., Tsai, S. Y., Tsai, M., & O’Malley, B. W. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.19.8832 · Cited by 330 · see citing works
Mechanism of Thyroid Hormone Action
Harvey, C. B., & Williams, G. R. (2002) · Thyroid · doi:10.1089/105072502760143791 · Cited by 306 · see citing works
Self-citationLong-Term Growth in Juvenile Acquired Hypothyroidism:
Rivkees, S. A., Bode, H. H., & Crawford, J. D. (1988) · New England Journal of Medicine · doi:10.1056/nejm198803103181003 · Cited by 272 · see citing works
Kaneshige, M., Kaneshige, K., Zhu, X.-G., Dace, A., Garrett, L. J., Carter, T. A., Kazlauskaite, R., Pankratz, D. G., Wynshaw-Boris, A. J., Refetoff, S., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.230285997 · Cited by 268 · see citing works
Self-citationThe molecular actions of thyroid hormone in bone
Duncan Bassett, J. H., & Williams, G. R. (2003) · Trends in Endocrinology & Metabolism · doi:10.1016/s1043-2760(03)00144-9 · Cited by 261 · see citing works
Self-citationWeiss, R. E., & Refetoff, S. (2000) · Reviews in Endocrine and Metabolic Disorders · doi:10.1023/a:1010072605757 · Cited by 257 · see citing works
Parrilla, R., Mixson, A. J., McPherson, J. A., McClaskey, J. H., & Weintraub, B. D. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115542 · Cited by 244 · see citing works
Srivastava, S., Weitzmann, M. N., Kimble, R. B., Rizzo, M., Zahner, M., Milbrandt, J., Ross, F. P., & Pacifici, R. (1998) · Journal of Clinical Investigation · doi:10.1172/jci4561 · Cited by 197 · see citing works
Multiple Mechanisms for Regulation of the Transcriptional Activity of Thyroid Hormone Receptors
Cheng, S.-Y. (2000) · Reviews in Endocrine and Metabolic Disorders · doi:10.1023/a:1010052101214 · Cited by 190 · see citing works
Self-citationRalston, S. H., Uitterlinden, A. G., Brandi, M. L., Balcells, S., Langdahl, B. L., Lips, P. T. A. M., Lorenc, R. S., Obermayer-Pietsch, B. M., Scollen, S., Bustamante, M., et al. (2006) · PLoS Medicine · doi:10.1371/journal.pmed.0030090 · Cited by 182 · see citing works
Farsetti, A., Desvergne, B., Hallenbeck, P. L., Robbins, J., & Nikodem, V. M. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)49603-8 · Cited by 167 · see citing works
Thyroid Hormone Excess Rather Than Thyrotropin Deficiency Induces Osteoporosis in Hyperthyroidism
Bassett, J. H. D., O’Shea, P. J., Sriskantharajah, S., Rabier, B., Boyde, A., Howell, P. G. T., Weiss, R. E., Roux, J.-P., Malaval, L., Clement-Lacroix, P., et al. (2007) · Molecular Endocrinology · doi:10.1210/me.2007-0033 · Cited by 167 · see citing works
Self-citation転写因子TF II Bとヒト甲状腺ホルモン受容体βとの結合は標的遺伝子の発現と甲状腺ホルモンによる活性化を仲介する
Baniahmad, A., Ha, I., Reinberg, D., Tsai, M., Tsai, M., & O’Malley, B. W. (1993) · Cited by 134 · see citing works
O’Shea, P. J., Harvey, C. B., Suzuki, H., Kaneshige, M., Kaneshige, K., Cheng, S.-Y., & Williams, G. R. (2003) · Molecular Endocrinology · doi:10.1210/me.2002-0296 · Cited by 131 · see citing works
Self-citationO’Shea, P. J., Bassett, J. H. D., Sriskantharajah, S., Ying, H., Cheng, S.-Y., & Williams, G. R. (2005) · Molecular Endocrinology · doi:10.1210/me.2005-0224 · Cited by 126 · see citing works
Self-citationSpecial Features of Graves' Disease in Early Childhood
Segni, M., Leonardi, E., Mazzoncini, B., Pucarelli, I., & Pasquino, A. M. (1999) · Thyroid · doi:10.1089/thy.1999.9.871 · Cited by 120 · see citing works
Thyroid Hormone Activates Fibroblast Growth Factor Receptor-1 in Bone
Stevens, D. A., Harvey, C. B., Scott, A. J., O’Shea, P. J., Barnard, J. C., Williams, A. J., Brady, G., Samarut, J., Chassande, O., & Williams, G. R. (2003) · Molecular Endocrinology · doi:10.1210/me.2003-0137 · Cited by 105 · see citing works
Self-citationTanabe, N., Maeno, M., Suzuki, N., Fujisaki, K., Tanaka, H., Ogiso, B., & Ito, K. (2005) · Life Sciences · doi:10.1016/j.lfs.2004.10.079 · Cited by 103 · see citing works
EFFECT OF THYROID HORMONE ON GROWTH
Weiss, R. E., & Refetoff, S. (1996) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(05)70349-2 · Cited by 98 · see citing works
A Novel Interaction between Thyroid Hormones and 1,25(OH)2D3 in Osteoclast Formation
Miura, M., Tanaka, K., Komatsu, Y., Suda, M., Yasoda, A., Sakuma, Y., Ozasa, A., & Nakao, K. (2002) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2002.6561 · Cited by 88 · see citing works
Brent, G. A., Williams, G. R., Harney, J. W., FORMAN, B. M., Samuels, H. H., Moore, D. D., & Larsen, P. R. (1992) · Molecular Endocrinology · doi:10.1210/mend.6.4.1584220 · Cited by 84 · see citing works
Self-citationSiddiqi, A., Burrin, J., Wood, D. F., & Monson, J. (1998) · Journal of Endocrinology · doi:10.1677/joe.0.1570453 · Cited by 77 · see citing works
Ying, H., Suzuki, H., Zhao, L., Willingham, M. C., Meltzer, P. S., & Cheng, S.-Y. (2003) · PubMed · Cited by 76 · see citing works
Self-citationpSV00CAT: low background CAT plasmid
Araki, E., Shimada, F., Shichiri, M., Mori, M., & Ebina, Y. (1988) · Nucleic Acids Research · doi:10.1093/nar/16.4.1627 · Cited by 73 · see citing works
Zhang, X., Kaneshige, M., Kamiya, Y., Kaneshige, K., McPhie, P., & Cheng, S.-Y. (2002) · Molecular Endocrinology · doi:10.1210/me.2002-0080 · Cited by 55 · see citing works
Self-citationO'Shea, P. J., Bassett, J. H. D., Cheng, S.-Y., & Williams, G. R. (2006) · Nuclear Receptor Signaling · doi:10.1621/nrs.04011 · Cited by 53 · see citing works
Self-citationKamiya, Y., Zhang, X., Ying, H., Kato, Y., Willingham, M. C., Xu, J., O’Malley, B. W., & Cheng, S.-Y. (2003) · Endocrinology · doi:10.1210/en.2003-0239 · Cited by 42 · see citing works
Self-citationHarvey, C. B., Bassett, J. H. D., Maruvada, P., Yen, P. M., & Williams, G. R. (2007) · Endocrinology · doi:10.1210/en.2006-1248 · Cited by 41 · see citing works
Self-citationCharacterization of the promoter region of the murine fibroblast growth factor receptor 1 gene
Saito, H., Kouhara, H., Kasayama, S., Kishimoto, T., & Sato, B. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(92)90537-u · Cited by 35 · see citing works
Zhu, X., McPhie, P., Lin, K., & Cheng, S.-Y. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.14.9048 · Cited by 34 · see citing works
Self-citationVoz, M. L., Peers, B., Wiedig, M., Jacquemin, P., Belayew, A., & MARTIAL, J. A. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.9.3991-3997.1992 · Cited by 33 · see citing works
Liu, J., Yang, H., Liu, W., Cao, X., & Feng, X. (2005) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20569 · Cited by 33 · see citing works
Bhat, M. K., McPhie, P., Ting, Y.-T., Zhu, X., & Cheng, S.-Y. (1995) · Biochemistry · doi:10.1021/bi00033a034 · Cited by 31 · see citing works
Self-citationIn vivo transcription factor recruitment during thyroid hormone receptor-mediated activation
Kim, M. K., Lee, J., & Chung, J. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.18.10092 · Cited by 30 · see citing works
Parakati, R., & DiMario, J. X. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m410744200 · Cited by 27 · see citing works
Kitagawa, S., Obata, T., Willingham, M. C., & Cheng, S.-Y. (1987) · Endocrinology · doi:10.1210/endo-120-6-2591 · Cited by 26 · see citing works
Self-citationLin, H., Kaneshige, M., Zhao, L., Zhang, X., Hanover, J. A., & Cheng, S.-Y. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104320200 · Cited by 18 · see citing works
Self-citationGonzález‐Manchón, C., Ayuso, M. S., & Parrilla, R. (1999) · Gene · doi:10.1016/s0378-1119(98)00543-5 · Cited by 9 · see citing works
Saito, H., Kouhara, H., Harada, T., Miyake, S., Sugiyama, H., Kishimoto, T., & Sato, B. (1994) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1994.1145 · Cited by 7 · see citing works
Flagged first, then by citations
1 of the 47 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Bianco, A. C., Anderson, G., Forrest, D., Galton, V. A., Gereben, B., Kim, B. W., Kopp, P. A., Liao, X. H., Obregon, M. J., Peeters, R. P., et al. (2014) · Thyroid · doi:10.1089/thy.2013.0109 · Cited by 205 · see citing works
Self-citationBassett, J. H. D., Williams, A. J., Murphy, E., Boyde, A., Howell, P. G., Swinhoe, R., Archanco, M., Flamant, F., Samarut, J., Costagliola, S., et al. (2008) · Molecular Endocrinology · doi:10.1210/me.2007-0221 · Cited by 110 · see citing works
Self-citationThe skeletal phenotypes of TRα and TRβ mutant mice
Bassett, J. H. D., & Williams, G. R. (2008) · Journal of Molecular Endocrinology · doi:10.1677/jme-08-0142 · Cited by 82 · see citing works
Self-citationType I Collagen Structure, Synthesis, and Regulation
Bou–Gharios, G., & Crombrugghe, B. D. (2008) · Elsevier eBooks · doi:10.1016/b978-0-12-373884-4.00034-3 · Cited by 60 · see citing works
Role of thyroid hormones in craniofacial development
Leitch, V. D., Bassett, J. H. D., & Williams, G. R. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0304-5 · Cited by 51 · see citing works
Self-citationGuigon, C. J., Kim, D. W., Zhu, X., Zhao, L., & Cheng, S.-Y. (2010) · Endocrinology · doi:10.1210/en.2010-0475 · Cited by 36 · see citing works
Self-citationType I collagen structure, synthesis, and regulation
Bou–Gharios, G., Abraham, D., & Crombrugghe, B. D. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-814841-9.00013-0 · Cited by 31 · see citing works
Searcy, B. T., Beckstrom‐Sternberg, S. M., Beckstrom‐Sternberg, J. S., Stafford, P., Schwendiman, A. L., Soto-Pena, J., Owen, M. C., Ramirez, C., Phillips, J., Veldhoen, N., et al. (2012) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2011.12.036 · Cited by 29 · see citing works
Szarama, K. B., Gavara, N., Petralia, R. S., Chadwick, R. S., & Kelley, M. W. (2013) · BMC Developmental Biology · doi:10.1186/1471-213x-13-6 · Cited by 19 · see citing works
da Silva, R. A., Andrade, A. F. D. C., Feltran, G. D. S., Fernandes, C. J. D. C., de Assis, R. I. F., Ferreira, M. R., Andia, D. C., & Zambuzzi, W. F. (2018) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2018.08.008 · Cited by 18 · see citing works
Identification of thyroid hormone receptor binding sites in developing mouse cerebellum
Gagné, R., Green, J. R., Dong, H., Wade, M. G., & Yauk, C. L. (2013) · BMC Genomics · doi:10.1186/1471-2164-14-341 · Cited by 16 · see citing works
Role of diabetes- and obesity-related protein in the regulation of osteoblast differentiation
Linares, G. R., Xing, W., Burghardt, H. E., Baumgartner, B. G., Chen, S., Ricart, W., Fernández‐Real, J. M., Zorzano, A., & Mohan, S. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00065.2011 · Cited by 12 · see citing works
Wang, R., Zhong, J., Pan, X., Su, Z., Xu, Y., Zhang, M., Chen, X., Chen, N., Yu, T., & Zhou, Q. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04718-y · Cited by 7 · see citing works
Chronic Excess Iodine Intake Inhibits Bone Reconstruction Leading to Osteoporosis in Rats
Zhang, Y., Zhao, X., Zhao, N., Meng, H., Zhang, Z., Song, Y., Shan, L., Zhang, X., Zhang, W., & Sang, Z. (2024) · Journal of Nutrition · doi:10.1016/j.tjnut.2024.02.005 · Cited by 7 · see citing works
Cheng, J., Cao, X., Peng, S., Wang, X., Li, Z., Elnour, I. E., Huang, Y., Lan, X., & Chen, H. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.29711 · Cited by 5 · see citing works
Targeting FGFR for the Treatment of Breast Cancer
Ali, R., Akhand, S. S., & Wendt, M. K. (2017) · Resistance to targeted anti-cancer therapeutics · doi:10.1007/978-3-319-70142-4_5 · Cited by 3 · see citing works
Strengthening the Role of PSMC5 as a Potential Gene Associated with Neurodevelopmental Disorders
Vinci, M., Musumeci, A., Papa, C., Ragalmuto, A., Saccone, S., Federico, C., Greco, D., Greco, V., Calì, F., & Treccarichi, S. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26136386 · Cited by 2 · see citing works
“Although the thyroid hormone T3 modulates FGFR1 signaling [18–20], no explicit genotype-phenotype correlation links this variant to thyroid dysfunction.”
Endocrinology of Bone and Growth Disorders
Farquharson, C., Stephen, L. A., & Wong, S. C. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820472-6.00086-4 · Cited by 3 · see citing works
Thyroid and Thyroid Hormone: Normal Function, Diseases, Disorders, Emerging Therapeutics
Stern, P. H. (2012) · Springer eBooks · doi:10.1007/978-1-4471-2745-1_4
Novel Molecules that Regulate Bone Formation and Bone Resorption
Linares, G. R. (2011) · The Scholars Repository - LLU (Loma Linda University)
Li, R., Yang, Y., Xu, X., Li, R., Yang, Y., Zhang, Z., & Guo, C. (2020) · International Conference on Biological Information and Biomedical Engineering (BIBE) · doi:10.1145/3403782.3403800
Wang, R., Zhong, J., Pan, X., Su, Z., Xu, Y., Zhang, M., Chen, X., Chen, N., Yu, T., & Zhou, Q. (2023) · Figshare · doi:10.6084/m9.figshare.24628126
- Authors
- O’Shea, P. J., Guigon, C. J., Williams, G. R., & Cheng, S.-Y.
- Affiliations
- Gene Regulation Section (P.J.O, C.J.G., S.C.), Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4264;
- Imperial College London (GB)
- National Institutes of Health (US)
- Corresponding author
- Cheng, Sheue-yann
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2007-12-01
- Volume
- 148
- Issue
- 12
- Pages
- 5966-5976
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2054567390
- Cited by
- 22
- References
- 47
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 1 · 2013: 3 · 2012: 2
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission
- National Institutes of Health
- National Cancer Institute (20892)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- FGFR1, thyroid hormones, thyroid hormone response element, thyroid hormone receptor beta 1, thyroid hormone receptor alpha 1, osteoblasts, bone formation, transcriptional regulation, calvarial osteoblasts
- MeSH terms
- Animals, Base Sequence, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Gene Expression Regulation, Molecular Sequence Data, Osteoblasts, Promoter Regions, Genetic, Protein Binding, Thyroid Hormones, Reverse Transcriptase Polymerase Chain Reaction, Response Elements, Electrophoretic Mobility Shift Assay, Thyroid Hormone Receptors alpha, Thyroid Hormone Receptors beta, Mice, Receptor, Fibroblast Growth Factor, Type 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
