Transgenic Mice Overexpressing Human Fibroblast Growth Factor 23 (R176Q) Delineate a Putative Role for Parathyroid Hormone in Renal Phosphate Wasting Disorders
Abstract
Fibroblast growth factor 23 (FGF23) is a recently characterized protein likely involved in the regulation of serum phosphate homeostasis. Increased circulating levels of FGF23 have been reported in patients with renal phosphate-wasting disorders, but it is unclear whether FGF23 is the direct mediator responsible for the decreased phosphate transport at the proximal renal tubules and the altered vitamin D metabolism associated with these states. To examine this question, we generated transgenic mice expressing and secreting from the liver human FGF23 (R176Q), a mutant form that fails to be degraded by furin proteases. At 1 and 2 months of age, mice carrying the transgene recapitulated the biochemical (decreased urinary phosphate reabsorption, hypophosphatemia, low serum 1,25-dihydroxyvitamin D3) and skeletal (rickets and osteomalacia) alterations associated with these disorders. Unexpectantly, marked changes in parameters of calcium homeostasis were also observed, consistent with secondary hyperparathyroidism. Moreover, in the kidney the anticipated alterations in the expression of hydroxylases associated with vitamin D metabolism were not observed despite the profound hypophosphatemia and increased circulating levels of PTH, both major physiological stimuli for 1,25-dihydroxyvitamin D3 production. Our findings strongly support the novel concept that high circulating levels of FGF23 are associated with profound disturbances in the regulation of phosphate and vitamin D metabolism as well as calcium homeostasis and that elevated PTH levels likely also contribute to the renal phosphate wasting associated with these disorders.
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In the current study, elevated iFGF23 did not inhibit PTH secretion but rather PTH stimulated iFGF23, eventually to lower plasma Pi.
“suggesting that in the current study elevated iFGF23 did not inhibit PTH secretion but rather PTH stimulated iFGF23, eventually to lower plasma Pi [4, 39].”
From Controlled dietary phosphate loading in healthy young men elevates plasma phosphate and FGF23 levels (2025) · cites this paper as [4]
Cites
Osteoprotegerin: a novel secreted protein involved in the regulation of bone density.
Simonet, W. S., Lacey, D. L., Dunstan, C. R., Kelley, M., Chang, M.-S., Lüthy, R., Nguyen, H. Q., Wooden, S., Bennett, L., Boone, T., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80209-3 · Cited by 5,130 · see citing works
Shimada, T., Kakitani, M., Yamazaki, Y., Hasegawa, H., Takeuchi, Y., Fujita, T., Fukumoto, S., Tomizuka, K., & Yamashita, T. (2004) · Journal of Clinical Investigation · doi:10.1172/jci19081 · Cited by 1,503 · see citing works
Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23
White, K., Evans, W. E., O'Riordan, J., Speer, M., Econs, M., Lorenz-Depiereux, B., Grabowski, M., Meitinger, T., & Strom, T. (2000) · Nature Genetics · doi:10.1038/81664 · Cited by 1,467 · see citing works
Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia
Shimada, T., Mizutani, S., Muto, T., Yoneya, T., Hino, R., Takeda, S., Takeuchi, Y., Fujita, T., Fukumoto, S., & Yamashita, T. (2001) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.101545198 · Cited by 1,391 · see citing works
Shimada, T., Kakitani, M., Yamazaki, Y., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200419081 · Cited by 1,368 · see citing works
Francis, F., Hennig, S., Korn, B., Reinhardt, R., de Jong, P., Poustka, A. J., Lehrach, H. R., Rowe, P. S., Goulding, J. N., Summerfield, T. C., et al. (1995) · Nature Genetics · doi:10.1038/ng1095-130 · Cited by 1,095 · see citing works
Fibroblast Growth Factor 23 in Oncogenic Osteomalacia and X-Linked Hypophosphatemia
Jonsson, K. B., Zahradnik, R. J., Larsson, T. E., White, K. E., Sugimoto, T., Imanishi, Y., Yamamoto, T., Hampson, G., Koshiyama, H., Ljunggren, Ö., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa020881 · Cited by 904 · see citing works
NOMOGRAM FOR DERIVATION OF RENAL THRESHOLD PHOSPHATE CONCENTRATION
Walton, R. J., & Bijvoet, O. L. M. (1975) · The Lancet · doi:10.1016/s0140-6736(75)92736-1 · Cited by 892 · see citing works
Yamazaki, Y., Okazaki, R., Shibata, M., Hasegawa, Y., Satoh, K., Tajima, T., Takeuchi, Y., Fujita, T., Nakahara, K., Yamashita, T., et al. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021105 · Cited by 670 · see citing works
FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting
Riminucci, M., Collins, M. T., Fedarko, N. S., Cherman, N., Corsi, A., White, K. E., Waguespack, S. G., Gupta, A., Hannon, T. S., Econs, M. J., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci18399 · Cited by 656 · see citing works
León, A. L.-D., & Rojkind, M. (1985) · Journal of Histochemistry & Cytochemistry · doi:10.1177/33.8.2410480 · Cited by 607 · see citing works
Beck, L., Karaplis, A. C., Amizuka, N., Hewson, A. S., Ozawa, H., & Tenenhouse, H. S. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.9.5372 · Cited by 607 · see citing works
Self-citationRegulation of Fibroblastic Growth Factor 23 Expression but Not Degradation by PHEX
Liu, S., Guo, R., Simpson, L. G., Xiao, Z.-S., Burnham, C. E., & Quarles, L. D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304544200 · Cited by 505 · see citing works
Larsson, T. E., Marsell, R., Schipani, E., Ohlsson, C., Ljunggren, Ö., Tenenhouse, H. S., Jüppner, H., & Jonsson, K. B. (2004) · Endocrinology · doi:10.1210/en.2003-1768 · Cited by 497 · see citing works
Autosomal-dominant hypophosphatemic rickets (ADHR) mutations stabilize FGF-23
White, K. E., Carn, G., Lorenz‐Depiereux, B., Benet‐Pagès, A., Strom, T. M., & Econs, M. J. (2001) · Kidney International · doi:10.1046/j.1523-1755.2001.00064.x · Cited by 488 · see citing works
Shimada, T., Urakawa, I., Yamazaki, Y., Hasegawa, H., Hino, R., Yoneya, T., Takeuchi, Y., Fujita, T., Fukumoto, S., & Yamashita, T. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.12.102 · Cited by 429 · see citing works
Prié, D., Huart, V., Bakouh, N., Planelles, G., Dellis, O., Gérard, B., Hulin, P., Benqué-Blanchet, F., Silve, C., Grandchamp, B., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa020028 · Cited by 362 · see citing works
Serum FGF23 Levels in Normal and Disordered Phosphorus Homeostasis
Weber, T. J., Liu, S., Indridason, Ó. S., & Quarles, L. D. (2003) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2003.18.7.1227 · Cited by 353 · see citing works
FGF-23 Inhibits Renal Tubular Phosphate Transport and Is a PHEX Substrate
Bowe, A. E., Finnegan, R., de Beur, S. M. J., Cho, J., Levine, M. A., Kumar, R., & Schiavi, S. C. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.5084 · Cited by 339 · see citing works
FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization
Quarles, L. D. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00016.2003 · Cited by 335 · see citing works
Shigematsu, T., Kazama, J. J., Yamashita, T., Fukumoto, S., Hosoya, T., Gejyo, F., & Fukagawa, M. (2004) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2004.04.029 · Cited by 325 · see citing works
Econs, M. J., & McEnery, P. T. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.2.3765 · Cited by 298 · see citing works
Secreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent
Berndt, T. J., Craig, T. A., Bowe, A. E., Vassiliadis, J., Reczek, D., Finnegan, R., de Beur, S. M. J., Schiavi, S. C., & Kumar, R. (2003) · Journal of Clinical Investigation · doi:10.1172/jci18563 · Cited by 292 · see citing works
Bai, X., Miao, D., Goltzman, D., & Karaplis, A. C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210490200 · Cited by 274 · see citing works
Self-citationOctreotide Therapy for Tumor-Induced Osteomalacia
Seufert, J., Ebert, K., Müller, J. G., Eulert, J., Hendrich, C., Werner, E., Schütze, N., Schulz, G. V., Kenn, W., Richtmann, H., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa010839 · Cited by 233 · see citing works
Histochemical Localization of Alkaline Phosphatase Activity in Decalcified Bone and Cartilage
Miao, D., & Scutt, A. M. (2002) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215540205000305 · Cited by 225 · see citing works
Self-citationSimonet, W. S., Bucay, N., Lauer, S., & Taylor, J. M. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53085-4 · Cited by 212 · see citing works
Miao, D., Bai, X., Panda, D. K., McKee, M. D., Karaplis, A. C., & Goltzman, D. (2001) · Endocrinology · doi:10.1210/endo.142.2.7976 · Cited by 162 · see citing works
Self-citationTumor-induced osteomalacia and the regulation of phosphate homeostasis
Kumar, R. (2000) · Bone · doi:10.1016/s8756-3282(00)00334-3 · Cited by 149 · see citing works
Lipman, M. L., Panda, D. K., Bennett, H. P. J., Henderson, J. E., Shane, E. J., Shen, Y., Goltzman, D., & Karaplis, A. C. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.22.13729 · Cited by 135 · see citing works
Self-citationNEW PERSPECTIVES ON THE BIOLOGY AND TREATMENT OF X-LINKED HYPOPHOSPHATEMIC RICKETS
Carpenter, T. O. (1997) · Pediatric Clinics of North America · doi:10.1016/s0031-3955(05)70485-5 · Cited by 128 · see citing works
Oncogenic Osteomalacia — A Complex Dance of Factors
Carpenter, T. O. (2003) · New England Journal of Medicine · doi:10.1056/nejme030037 · Cited by 125 · see citing works
Sullivan, W., Carpenter, T. O., Glorieux, F. H., Travers, R., & Insogna, K. L. (1992) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.75.3.1517380 · Cited by 103 · see citing works
Skeletal Abnormalities in Pth-Null Mice Are Influenced by Dietary Calcium
Miao, D., He, B., Lanske, B., Bai, X., Tong, X., Hendy, G. N., Goltzman, D., & Karaplis, A. C. (2004) · Endocrinology · doi:10.1210/en.2003-1097 · Cited by 101 · see citing works
Self-citationBai, X., Miao, D., Panda, D., Grady, S., McKee, M. D., Goltzman, D., & Karaplis, A. C. (2002) · Molecular Endocrinology · doi:10.1210/me.2002-0113 · Cited by 100 · see citing works
Self-citationCampos, M., COUTURE, C., Hirata, I. Y., Juliano, M. A., Loisel, T. P., Crine, P., Juliano, L., Boileau, G., & Carmona, A. K. (2003) · Biochemical Journal · doi:10.1042/bj20030287 · Cited by 98 · see citing works
Parathyroid hormone regulates 25-hydroxyvitamin D 3 -24-hydroxylase mRNA by altering its stability
Zierold, C., Mings, J. A., & DeLuca, H. F. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.241516798 · Cited by 90 · see citing works
Hypophosphataemic Osteomalacia in Fibrous Dysplasia
Dent, C. E., & Gertner, J. M. (1976) · QJM · doi:10.1093/oxfordjournals.qjmed.a067471 · Cited by 88 · see citing works
Boileau, G., Tenenhouse, H. S., DesGroseillers, L., & Crine, P. (2001) · Biochemical Journal · doi:10.1042/bj3550707 · Cited by 82 · see citing works
Analysis of recombinant Phex: an endopeptidase in search of a substrate
Guo, R., Liu, S., Spurney, R. F., & Quarles, L. D. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.281.4.e837 · Cited by 81 · see citing works
Nocturnal hyperparathyroidism: a frequent feature of X-linked hypophosphatemia
Carpenter, T. O., Mitnick, M. A., Ellison, A. F., Smith, C., & Insogna, K. L. (1994) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.78.6.8200940 · Cited by 76 · see citing works
FGF23, hypophosphatemia, and rickets: Has phosphatonin been found?
Strewler, G. J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.111154898 · Cited by 70 · see citing works
Zierold, C., Reinholz, G. G., Mings, J. A., Prahl, J. M., & DeLuca, H. F. (2000) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.2000.1964 · Cited by 66 · see citing works
Blydt‐Hansen, T. D., Tenenhouse, H. S., & Goodyer, P. (1999) · Pediatric Nephrology · doi:10.1007/s004670050669 · Cited by 63 · see citing works
The enigma of hyperparathyroidism in hypophosphatemic rickets
Schmitt, C. P., & Mehls, O. (2004) · Pediatric Nephrology · doi:10.1007/s00467-004-1443-y · Cited by 60 · see citing works
Miao, D., & Scutt, A. M. (2002) · BMC Musculoskeletal Disorders · doi:10.1186/1471-2474-3-16 · Cited by 53 · see citing works
Self-citationNovel phosphate-regulating genes in the pathogenesis of renal phosphate wasting disorders
Tenenhouse, H. S., & Sabbagh, Y. (2002) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-002-0839-4 · Cited by 52 · see citing works
Tissue-Specific Targeting of the Pthrp Gene: The Generation of Mice with Floxed Alleles
He, B., Deckelbaum, R. A., Miao, D., Lipman, M. L., Pollak, M., Goltzman, D., & Karaplis, A. C. (2001) · Endocrinology · doi:10.1210/endo.142.5.8146 · Cited by 44 · see citing works
Self-citationAutonomous hyperparathyroidism in X‐linked hypophosphataemia
Knudtzon, J., Halse, J., Monn, E., Nesland, A., Nordal, K. P., Paus, P. N., Selp, M., Sund, S., & Sedall, G. (1995) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1995.tb01863.x · Cited by 43 · see citing works
Secondary Hyperparathyroidism in X-Linked Hypophosphatemic Mice*
Kiebzak, G. M., Roos, B. A., & Meyer, R. A. (1982) · Endocrinology · doi:10.1210/endo-111-2-650 · Cited by 41 · see citing works
Oncogenic Osteomalacia Caused by a Phosphaturic Mesenchymal Tumor of the Oral Cavity
Yang, I. M., Park, Y. K., Hyun, Y. J., Kim, D. Y., Woo, J., Kim, S. W., Kim, J., Kim, Y. S., & Choi, Y. K. (1997) · The Korean Journal of Internal Medicine · doi:10.3904/kjim.1997.12.1.89 · Cited by 27 · see citing works
Fujiwara, I., Aravindan, R. G., Horst, R. L., & Drezner, M. K. (2003) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2003.18.3.434 · Cited by 24 · see citing works
Meyer, R. A., Meyer, M. H., & Morgan, P. L. (1996) · Bone · doi:10.1016/8756-3282(95)00420-3 · Cited by 19 · see citing works
Is FGF23 the long sought after phosphaturic factor phosphatonin?
Silve, C. (2002) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/17.6.958 · Cited by 17 · see citing works
Studies in a patient with tumor-induced hypophosphatemic osteomalacia
Ryan, W. G., Gitelis, S., & Charters, J. R. (1986) · Calcified Tissue International · doi:10.1007/bf02555750 · Cited by 13 · see citing works
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The parathyroid is a target organ for FGF23 in rats
Ben‐Dov, I. Z., Galitzer, H., Lavi-Moshayoff, V., Goetz, R. M., Kuro‐o, M., Mohammadi, M., Sirkis, R., Naveh‐Many, T., & Silver, J. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32409 · Cited by 951 · see citing works
Gutiérrez, O. M., Isakova, T., Rhee, E. P., Shah, A., Holmes, J., Collerone, G., Diaeresis]ppner, H. J., & Wolf, M. S. (2005) · Journal of the American Society of Nephrology · doi:10.1681/asn.2005010052 · Cited by 920 · see citing works
FGF/FGFR signaling in health and disease
Xie, Y., Su, N., Yang, J., Tan, Q., Huang, S., Jin, M., Ni, Z., Zhang, B., Zhang, D., Luo, F., et al. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00222-7 · Cited by 904 · see citing works
Regulation of Phosphate Homeostasis by PTH, Vitamin D, and FGF23
Bergwitz, C., & Jüppner, H. (2010) · Annual Review of Medicine · doi:10.1146/annurev.med.051308.111339 · Cited by 741 · see citing works
Fibroblast Growth Factor 23 Is a Counter-Regulatory Phosphaturic Hormone for Vitamin D
Liu, S., Tang, W., Zhou, J., Stubbs, J. R., Luo, Q., Pi, M., & Quarles, L. D. (2006) · Journal of the American Society of Nephrology · doi:10.1681/asn.2005111185 · Cited by 641 · see citing works
Regulation and Function of the FGF23/Klotho Endocrine Pathways
Martin, A., David, V., & Quarles, L. D. (2012) · Physiological Reviews · doi:10.1152/physrev.00002.2011 · Cited by 595 · see citing works
Sitara, D., Razzaque, M., Hesse, M., Yoganathan, S., Taguchi, T., Erben, R., Jüppner, H., & Lanske, B. (2004) · Matrix Biology · doi:10.1016/j.matbio.2004.09.007 · Cited by 528 · see citing works
Pathogenic role of Fgf23 in Hyp mice
Liu, S., Zhou, J., Tang, W., Jiang, X., Rowe, D. W., & Quarles, L. D. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00008.2006 · Cited by 494 · see citing works
Bergwitz, C., Roslin, N. M., Tieder, M., Loredo‐Osti, J., Bastepe, M., Abu-Zahra, H., Frappier, D., Burkett, K. M., Carpenter, T. O., Anderson, D., et al. (2006) · The American Journal of Human Genetics · doi:10.1086/499409 · Cited by 485 · see citing works
Krajisnik, T., Björklund, P., Marsell, R., Ljunggren, Ö., Åkerström, G., Jonsson, K. B., Westin, G., & Larsson, T. E. (2007) · Journal of Endocrinology · doi:10.1677/joe-07-0267 · Cited by 473 · see citing works
Endocrine functions of bone in mineral metabolism regulation
Quarles, L. D. (2008) · Journal of Clinical Investigation · doi:10.1172/jci36479 · Cited by 459 · see citing works
The FGF23–Klotho axis: endocrine regulation of phosphate homeostasis
Razzaque, M. S. (2009) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2009.196 · Cited by 450 · see citing works
Gattineni, J., Bates, C. M., Twombley, K. E., Dwarakanath, V. N., Robinson, M. L., Goetz, R. M., Mohammadi, M., & Baum, M. G. (2009) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.90742.2008 · Cited by 439 · see citing works
Christakos, S., Ajibade, D. V., Dhawan, P., Fechner, A. J., & Mady, L. J. (2010) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2010.02.002 · Cited by 430 · see citing works
Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF23
Degirolamo, C., Sabbà, C., & Moschetta, A. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2015.9 · Cited by 424 · see citing works
Dietary Phosphorus Regulates Serum Fibroblast Growth Factor-23 Concentrations in Healthy Men
Antoniucci, D. M., Yamashita, T., & Portale, A. A. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0021 · Cited by 421 · see citing works
Shalhoub, V., Shatzen, E. M., Ward, S. C., Davis, J., Stevens, J. L., Bi, V., Renshaw, L., Hawkins, N., Wang, W., Chen, C., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci61405 · Cited by 417 · see citing works
How Fibroblast Growth Factor 23 Works
Liu, S., & Quarles, L. D. (2007) · Journal of the American Society of Nephrology · doi:10.1681/asn.2007010068 · Cited by 407 · see citing works
Vitamin D receptor-independent FGF23 actions in regulating phosphate and vitamin D metabolism
Shimada, T., Yamazaki, Y., Takahashi, M., Hasegawa, H., Urakawa, I., Oshima, T., Ono, K., Kakitani, M., Tomizuka, K., Fujita, T., et al. (2005) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00474.2004 · Cited by 359 · see citing works
Razzaque, M. S., Sitara, D., Taguchi, T., St‐Arnaud, R., & Lanske, B. (2006) · The FASEB Journal · doi:10.1096/fj.05-5432fje · Cited by 345 · see citing works
Hasegawa, H., Nagano, N., Urakawa, I., Yamazaki, Y., Iijima, K., Fujita, T., Yamashita, T., Fukumoto, S., & Shimada, T. (2010) · Kidney International · doi:10.1038/ki.2010.313 · Cited by 339 · see citing works
Fibroblast growth factor 23 is not associated with and does not induce arterial calcification
Scialla, J. J., Lau, W. L., Reilly, M. P., Isakova, T., Yang, H.-Y. L., Crouthamel, M. H., Chavkin, N. W., Rahman, M., WAHL, P. W., Amaral, A. P., et al. (2013) · Kidney International · doi:10.1038/ki.2013.3 · Cited by 333 · see citing works
Forging Forward with 10 Burning Questions on FGF23 in Kidney Disease
Wolf, M. (2010) · Journal of the American Society of Nephrology · doi:10.1681/asn.2009121293 · Cited by 306 · see citing works
Role of FGF23 in vitamin D and phosphate metabolism: Implications in chronic kidney disease
Quarles, L. D. (2012) · Experimental Cell Research · doi:10.1016/j.yexcr.2012.02.027 · Cited by 299 · see citing works
Khundmiri, S. J., Murray, R. D., & Lederer, E. D. (2016) · Comprehensive physiology · doi:10.1002/cphy.c140071 · Cited by 352 · see citing works
Role of FGF/FGFR signaling in skeletal development and homeostasis: learning from mouse models
Su, N. Y., Jin, M. Y., & Chen, L. (2014) · Bone Research · doi:10.1038/boneres.2014.3 · Cited by 291 · see citing works
Mechanism of Bone MineralizationPreprint
Murshed, M. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a031229 · Cited by 284 · see citing works
FGF23 and its role in X-linked hypophosphatemia-related morbidity
Beck‐Nielsen, S. S., Zulf Mughal, M., Haffner, D., Nilsson, O., Levtchenko, E. N., Ariceta, G., Collantes, C. D. L., Schnabel, D., Jandhyala, R., & Mäkitie, O. (2019) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-019-1014-8 · Cited by 288 · see citing works
Skeletal secretion of FGF-23 regulates phosphate and vitamin D metabolism
Quarles, L. D. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.218 · Cited by 268 · see citing works
Therapeutic Effects of Anti-FGF23 Antibodies in Hypophosphatemic Rickets/Osteomalacia
Aono, Y., Yamazaki, Y., Yasutake, J., Kawata, T., Hasegawa, H., Urakawa, I., Fujita, T., Wada, M., Yamashita, T., Fukumoto, S., et al. (2009) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.090509 · Cited by 264 · see citing works
Wang, H., Yoshiko, Y., Yamamoto, R., Minamizaki, T., Kozai, K., Tanne, K., Aubin, J. E., & Maeda, N. (2008) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.080220 · Cited by 263 · see citing works
Novel Mechanisms in the Regulation of Phosphorus Homeostasis
Berndt, T. J., & Kumar, R. (2009) · Physiology · doi:10.1152/physiol.00034.2008 · Cited by 257 · see citing works
Nakatani, T., Sarraj, B., Ohnishi, M., Densmore, M., Taguchi, T., Goetz, R. M., Mohammadi, M., Lanske, B., & Razzaque, M. S. (2008) · The FASEB Journal · doi:10.1096/fj.08-114397 · Cited by 256 · see citing works
Martin, A., Liu, S., David, V., Li, H., Karydis, A., Feng, J. Q., & Quarles, L. D. (2011) · The FASEB Journal · doi:10.1096/fj.10-177816 · Cited by 254 · see citing works
Brownstein, C. A., Adler, F., Nelson-Williams, C. J., Iijima, J., Li, P., Imura, A., Nabeshima, Y., Reyes‐Múgica, M., Carpenter, T. O., & Lifton, R. P. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712361105 · Cited by 239 · see citing works
Razzaque, M. S., & Lanske, B. (2007) · Journal of Endocrinology · doi:10.1677/joe-07-0095 · Cited by 234 · see citing works
“Phosphatonins” and the regulation of phosphorus homeostasis
Berndt, T. J., Schiavi, S. C., & Kumar, R. (2005) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00072.2005 · Cited by 227 · see citing works
A Novel Recessive Mutation in Fibroblast Growth Factor-23 Causes Familial Tumoral Calcinosis
Larsson, T. E., Yu, X., Davis, S. I., Draman, M. S., Mooney, S. D., Cullen, M. J., & White, K. E. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-2238 · Cited by 221 · see citing works
Regulation of vitamin D metabolism
Henry, H. L. (2011) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2011.05.003 · Cited by 213 · see citing works
Analysis of the Biochemical Mechanisms for the Endocrine Actions of Fibroblast Growth Factor-23
Yu, X., Ibrahimi, O. A., Goetz, R. M., Zhang, F., Davis, S. I., Garringer, H. J., Linhardt, R. J., Ornitz, D. M., Mohammadi, M., & White, K. E. (2005) · Endocrinology · doi:10.1210/en.2005-0670 · Cited by 213 · see citing works
Hesse, M., Fröhlich, L. F., Zeitz, U., Lanske, B., & Erben, R. G. (2006) · Matrix Biology · doi:10.1016/j.matbio.2006.10.003 · Cited by 198 · see citing works
Anti-FGF23 Neutralizing Antibodies Show the Physiological Role and Structural Features of FGF23
Yamazaki, Y., Tamada, T., Kasai, N., Urakawa, I., Aono, Y., Hasegawa, H., Fujita, T., Kuroki, R., Yamashita, T., Fukumoto, S., et al. (2008) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.080417 · Cited by 195 · see citing works
Post-transplant hypophosphatemia: Tertiary ‘Hyper-Phosphatoninism’?
Bhan, I., Shah, A., Holmes, J., Isakova, T., Gutiérrez, O. M., Burnett‐Bowie, S. M., Jüppner, H., & Wolf, M. S. (2006) · Kidney International · doi:10.1038/sj.ki.5001788 · Cited by 193 · see citing works
FGF23 Concentrations Vary With Disease Status in Autosomal Dominant Hypophosphatemic Rickets
Imel, E. A., Hui, S. L., & Ecibs, M. J. (2007) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.070107 · Cited by 183 · see citing works
White, K. E., Larsson, T. E., & Econs, M. J. (2006) · Endocrine Reviews · doi:10.1210/er.2005-0019 · Cited by 177 · see citing works
Relevance of vitamin D in reproduction
Luk, J., Torrealday, S., Perry, G. N., & Pal, L. (2012) · Human Reproduction · doi:10.1093/humrep/des248 · Cited by 175 · see citing works
Role of the vitamin D receptor in FGF23 action on phosphate metabolism
Inoue, Y., Segawa, H., Kaneko, I., Yamanaka, S., Kusano, K., Kawakami, E., Furutani, J., Ito, M., Kuwahata, M., Saitô, H., et al. (2005) · Biochemical Journal · doi:10.1042/bj20041799 · Cited by 168 · see citing works
FGF23–parathyroid interaction: implications in chronic kidney disease
Komaba, H., & Fukagawa, M. (2009) · Kidney International · doi:10.1038/ki.2009.466 · Cited by 165 · see citing works
Physiological regulation of phosphate by vitamin D, parathyroid hormone (PTH) and phosphate (Pi)
Jacquillet, G., & Unwin, R. J. (2018) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-018-2231-z · Cited by 158 · see citing works
Shalhoub, V., Ward, S. C., Sun, B.-C., Stevens, J. L., Renshaw, L., Hawkins, N., & Richards, W. G. (2011) · Calcified Tissue International · doi:10.1007/s00223-011-9501-5 · Cited by 157 · see citing works
Sitara, D., Razzaque, M. S., St‐Arnaud, R., Huang, W. Y., Taguchi, T., Erben, R. G., & Lanske, B. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.060329 · Cited by 153 · see citing works
Wöhrle, S., Bonny, O., Beluch, N., Gaulis, S., Stamm, C., Scheibler, M., Müller, M. M., Kinzel, B., Thuery, A., Brueggen, J., et al. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.478 · Cited by 152 · see citing works
Yu, X., Sabbagh, Y., Davis, S. I., Demay, M. B., & White, K. E. (2005) · Bone · doi:10.1016/j.bone.2005.03.002 · Cited by 149 · see citing works
Targeted Deletion of Klotho in Kidney Distal Tubule Disrupts Mineral Metabolism
Olauson, H., Lindberg, K., Amin, R., Jia, T., Wernerson, A. M., Andersson, G. N., & Larsson, T. E. (2012) · Journal of the American Society of Nephrology · doi:10.1681/asn.2012010048 · Cited by 148 · see citing works
Determination of the Elimination Half-Life of Fibroblast Growth Factor-23
Khosravi, A., Peck, C. M. C., Kelly, M. H., Chang, R., Royal, R. E., Sherry, R. M., Wodajo, F. M., Fedarko, N. S., & Collins, M. T. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2865 · Cited by 147 · see citing works
Cinacalcet in the Management of Tumor-Induced Osteomalacia
Geller, J. L., Khosravi, A., Kelly, M. H., Riminucci, M., Adams, J. S., & Collins, M. T. (2007) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.070304 · Cited by 146 · see citing works
Hypervitaminosis D and premature aging: lessons learned from Fgf23 and Klotho mutant mice
Razzaque, M. S., & Lanske, B. (2006) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2006.05.002 · Cited by 145 · see citing works
Pathogenic role of Fgf23 in Dmp1 -null mice
Liu, S., Zhou, J., Tang, W., Menard, R., Feng, J. Q., & Quarles, L. D. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90201.2008 · Cited by 144 · see citing works
Correlation between hyperphosphatemia and type II Na-Pi cotransporter activity in klotho mice
Segawa, H., Yamanaka, S., Ohno, Y., Onitsuka, A., Shiozawa, K., Aranami, F., Furutani, J., Tomoe, Y., Ito, M., Kuwahata, M., et al. (2006) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00248.2006 · Cited by 144 · see citing works
FGF23-mediated regulation of systemic phosphate homeostasis: is Klotho an essential player?
Razzaque, M. S. (2008) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.90538.2008 · Cited by 143 · see citing works
FGFR3 and FGFR4 Do not Mediate Renal Effects of FGF23
Liu, S., Vierthaler, L., Tang, W., Zhou, J., & Quarles, L. D. (2008) · Journal of the American Society of Nephrology · doi:10.1681/asn.2007121301 · Cited by 143 · see citing works
The Role of Osteocytes in Age-Related Bone Loss
Jilka, R. L., & O’Brien, C. A. (2016) · Current Osteoporosis Reports · doi:10.1007/s11914-016-0297-0 · Cited by 136 · see citing works
Kharitonenkov, A. (2009) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2009.07.001 · Cited by 133 · see citing works
Fibroblast Growth Factor-23 Mutants Causing Familial Tumoral Calcinosis Are Differentially Processed
Larsson, T. E., Davis, S. I., Garringer, H. J., Mooney, S. D., Draman, M. S., Cullen, M. J., & White, K. E. (2005) · Endocrinology · doi:10.1210/en.2005-0431 · Cited by 134 · see citing works
Murali, S. K., Andrukhova, O., Clinkenbeard, E. L., White, K. E., & Erben, R. G. (2016) · PLoS Biology · doi:10.1371/journal.pbio.1002427 · Cited by 131 · see citing works
Liu, S., Gupta, A., & Quarles, L. D. (2007) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0b013e3281ca6ffd · Cited by 124 · see citing works
New Aspect of Renal Phosphate Reabsorption: The Type IIc Sodium-Dependent Phosphate Transporter
Miyamoto, K., Ito, M., Tatsumi, S., Kuwahata, M., & Segawa, H. (2007) · American Journal of Nephrology · doi:10.1159/000107069 · Cited by 122 · see citing works
Quinn, S. J., Thomsen, A. R. B., Pang, J. L., Kantham, L., Bräuner-Osborne, H., Pollak, M., Goltzman, D., & Brown, E. M. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00460.2012 · Cited by 115 · see citing works
Self-citationClinical relevance of FGF-23 in chronic kidney disease
Seiler, S., Heine, G. H., & Fliser, D. (2009) · Kidney International · doi:10.1038/ki.2009.405 · Cited by 113 · see citing works
Bergwitz, C., & Miyamoto, K. (2018) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-018-2184-2 · Cited by 113 · see citing works
Bone Formation Regulates Circulating Concentrations of Fibroblast Growth Factor 23
Samadfam, R., Richard, C., Nguyen‐Yamamoto, L., Bolivar, I., & Goltzman, D. (2009) · Endocrinology · doi:10.1210/en.2009-0472 · Cited by 106 · see citing works
Self-citationStrom, T. M., & Jüppner, H. (2008) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0b013e3282fd6e5b · Cited by 106 · see citing works
Indirect Regulation of PTH by Estrogens May Require FGF23
Carrillo‐López, N., Román‐García, P., Rebollar, A. R., Martín, J. L. F., Naves‐Díaz, M., & Cannata-Andía, J. B. (2009) · Journal of the American Society of Nephrology · doi:10.1681/asn.2008121258 · Cited by 106 · see citing works
Increased Osteopontin Contributes to Inhibition of Bone Mineralization in FGF23-Deficient Mice
Yuan, Q., Jiang, Y., Zhao, X., Sato, T., Densmore, M., Schüler, C., Erben, R. G., McKee, M. D., & Lanske, B. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2079 · Cited by 102 · see citing works
Imel, E. A., & Econs, M. J. (2005) · Journal of the American Society of Nephrology · doi:10.1681/asn.2005050573 · Cited by 100 · see citing works
Molecular pathology of the fibroblast growth factor family
Krejci, P., Procházková, J., Bryja, V., Kozubík, A., & Wilcox, W. R. (2009) · Human Mutation · doi:10.1002/humu.21067 · Cited by 99 · see citing works
Fibroblast Growth Factor-23 Is Regulated by 1α,25-Dihydroxyvitamin D
Collins, M. T., Lindsay, J. R., Jain, A., Kelly, M. H., Peck, C. M. C., Weinstein, L. S., Liu, J., Fedarko, N. S., & Winer, K. K. (2005) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.050718 · Cited by 97 · see citing works
Compound deletion of Fgfr3 and Fgfr4 partially rescues the Hyp mouse phenotype
Li, H., Martin, A., David, V., & Quarles, L. D. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00499.2010 · Cited by 96 · see citing works
Vitamin D signaling in osteocytes: Effects on bone and mineral homeostasis
Lieben, L., & Carmeliet, G. (2012) · Bone · doi:10.1016/j.bone.2012.10.007 · Cited by 95 · see citing works
Gene expression analysis of kidneys from transgenic mice expressing fibroblast growth factor-23
Marsell, R., Krajisnik, T., Göransson, H., Ohlsson, C., Ljunggren, Ö., Larsson, T. E., & Jonsson, K. B. (2007) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfm672 · Cited by 94 · see citing works
Christakos, S., Ajibade, D. V., Dhawan, P., Fechner, A. J., & Mady, L. J. (2012) · Rheumatic Disease Clinics of North America · doi:10.1016/j.rdc.2012.03.003 · Cited by 92 · see citing works
Liu, S., Rowe, P. S., Vierthaler, L., Zhou, J., & Quarles, L. D. (2007) · Journal of Endocrinology · doi:10.1677/joe.1.07059 · Cited by 92 · see citing works
Up-regulation of FGF23 release by aldosterone
Zhang, B., Umbach, A. T., Chen, H., Yan, J., Fakhri, H., Fajol, A., Salker, M. S., Spichtig, D., Daryadel, A., Wagner, C. A., et al. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.01.034 · Cited by 91 · see citing works
New insights into NPP1 function: Lessons from clinical and animal studies
Mackenzie, N. C. W., Huesa, C., Rutsch, F., & MacRae, V. E. (2012) · Bone · doi:10.1016/j.bone.2012.07.014 · Cited by 86 · see citing works
Liu, S., Tang, W., Zhou, J., Vierthaler, L., & Quarles, L. D. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00396.2007 · Cited by 86 · see citing works
In vivo evidence for a limited role of proximal tubular Klotho in renal phosphate handling
Ide, N., Olauson, H., Sato, T., Densmore, M., Wang, H., Hanai, J., Larsson, T. E., & Lanske, B. (2016) · Kidney International · doi:10.1016/j.kint.2016.04.009 · Cited by 86 · see citing works
Schoppet, M., Hofbauer, L. C., Brinskelle-Schmal, N., Varennes, A., Goudable, J., Richard, M., Hawa, G., Chapurlat, R. D., & Szulc, P. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-2836 · Cited by 81 · see citing works
Phosphaturic action of fibroblast growth factor 23 in Npt2 null mice
Tomoe, Y., Segawa, H., Shiozawa, K., Kaneko, I., Tominaga, R., Hanabusa, E., Aranami, F., Furutani, J., Kuwahara, S., Tatsumi, S., et al. (2010) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00375.2009 · Cited by 78 · see citing works
Biology of Fibroblast Growth Factor 23: From Physiology to PathologyPreprint
Courbebaisse, M., & Lanske, B. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a031260 · Cited by 81 · see citing works
Phosphate homeostasis disorders
Christov, M., & Jüppner, H. (2018) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2018.06.004 · Cited by 79 · see citing works
Bone cells and the mechanisms of bone remodelling
Teti, A. M. (2012) · Frontiers in Bioscience-Elite · doi:10.2741/e543 · Cited by 78 · see citing works
Portale, A. A., & Perwad, F. (2009) · Springer eBooks · doi:10.1007/978-3-540-76341-3_10 · Cited by 78 · see citing works
FGF23 or PTH: which comes first in CKD ?
Isakova, T., & Wolf, M. S. (2010) · Kidney International · doi:10.1038/ki.2010.281 · Cited by 77 · see citing works
Nguyen‐Yamamoto, L., Karaplis, A. C., St‐Arnaud, R., & Goltzman, D. (2016) · Journal of the American Society of Nephrology · doi:10.1681/asn.2016010066 · Cited by 76 · see citing works
Self-citationHensel, N., Schön, A., Konen, T., Lübben, V., Förthmann, B., Baron, O., Grothe, C., Leifheit‐Nestler, M., Claus, P., & Haffner, D. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13585 · Cited by 75 · see citing works
Regulation of fibroblast growth factor 23 ( FGF 23) in health and disease
Bär, L., Stournaras, C., Lang, F. J. W., & Föller, M. (2019) · FEBS Letters · doi:10.1002/1873-3468.13494 · Cited by 74 · see citing works
Vitamin D metabolism in the kidney: Regulation by phosphorus and fibroblast growth factor 23
Perwad, F., & Portale, A. A. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.08.030 · Cited by 74 · see citing works
Fibroblast Growth Factor 23/Klotho Axis in Chronic Kidney Disease
Nitta, K., Nagano, N., & Tsuchiya, K. (2014) · Nephron Clinical Practice · doi:10.1159/000365787 · Cited by 72 · see citing works
Hyperphosphatemic familial tumoral calcinosis (FGF23, GALNT3 and αKlotho)
Farrow, E., Imel, E. A., & White, K. E. (2011) · Best Practice & Research Clinical Rheumatology · doi:10.1016/j.berh.2011.10.020 · Cited by 74 · see citing works
Premature aging in klotho mutant mice: Cause or consequence?
Lanske, B., & Razzaque, M. S. (2007) · Ageing Research Reviews · doi:10.1016/j.arr.2007.02.002 · Cited by 72 · see citing works
- Authors
- Bai, X., Miao, D., Li, J., Goltzman, D., & Karaplis, A. C.
- Affiliations
- Jewish General Hospital (CA)
- McGill University Health Centre (CA)
- Corresponding author
- Karaplis, Andrew C.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2004-11-01
- Volume
- 145
- Issue
- 11
- Pages
- 5269-5279
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2144414222
- Cited by
- 329
- References
- 55
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 3 · 2023: 7 · 2022: 9 · 2021: 7 · 2020: 9 · 2019: 11 · 2018: 17 · 2017: 12 · 2016: 25 · 2015: 11 · 2014: 11 · 2013: 13 · 2012: 33
- FWCI
- 13.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Canadian Institutes of Health Research
- National Cancer Institute
- Canadian Arthritis Network
- Topics
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
- Health Sciences › Medicine › Nephrology › Renal function and acid-base balance
- Keywords
- fibroblast growth factor 23, parathyroid hormone, renal phosphate wasting, hypophosphatemia, vitamin D metabolism, 1,25-dihydroxyvitamin D3, secondary hyperparathyroidism, calcium homeostasis, osteomalacia, rickets, transgenic mice, furin protease
- MeSH terms
- Fibroblast Growth Factor-23, Animals, Bone and Bones, Calcium, Female, Fibroblast Growth Factors, Carcinoma, Hepatocellular, Humans, Hypophosphatemia, Familial, Kidney Tubules, Proximal, Male, Mice, Transgenic, Osteomalacia, Parathyroid Hormone, Phosphates, Pregnancy, Vitamin D, Gene Expression, Cell Line, Tumor, Mice
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