The role of vitamin D in the FGF23, klotho, and phosphate bone-kidney endocrine axis

Reviews in Endocrine and Metabolic Disorders

Volumn 13, Issue 1, 2012, Pages 57-69

  Haussler, Mark R ^a   Whitfield, G Kerr ^a   Kaneko, Ichiro ^a,b   Forster, Ryan ^b   Saini, Rimpi ^b   Hsieh, Jui Cheng ^a   Haussler, Carol A ^a   Jurutka, Peter W ^a,b  

^a UNIVERSITY OF ARIZONA COLLEGE OF MEDICINE   (United States)

^b ARIZONA STATE UNIVERSITY   (United States)

Author keywords

1,25 dihydroxyvitamin D hormone; Autosomal dominant hypophosphatemic rickets; Phosphate homeostasis; Retinoid X receptor; Tumor induced osteomalacia; Tumoral calcinosis; Vitamin D receptor; X linked hypophosphatemic rickets

Indexed keywords

CALCITRIOL; CURCUMIN; CYTOCHROME P450; CYTOCHROME P450 24A1; CYTOCHROME P450 27B1; FIBROBLAST GROWTH FACTOR 23; KLOTHO PROTEIN; LEPTIN; PHOSPHATE; RETINOID X RECEPTOR; UNCLASSIFIED DRUG; VITAMIN D; VITAMIN D RECEPTOR;

AGING; BONE DENSITY; BONE DISEASE; CALCIUM METABOLISM; DETOXIFICATION; ENZYME SYNTHESIS; GENE; GENETIC CODE; GENETIC TRANSCRIPTION; HUMAN; KIDNEY DISEASE; NONHUMAN; OSTEOCYTE; PATHOPHYSIOLOGY; PHOSPHATE METABOLISM; PROTEIN INTERACTION; REVIEW; UPREGULATION; VITAMIN D RESPONSIVE ELEMENT;

ANIMALS; BONE AND BONES; FIBROBLAST GROWTH FACTORS; GLUCURONIDASE; HUMANS; KIDNEY; MODELS, BIOLOGICAL; RECEPTORS, CALCITRIOL; RETINOID X RECEPTORS; VITAMIN D;

EID: 84858128980     PISSN: 13899155     EISSN: 15732606     Source Type: Journal    
DOI: 10.1007/s11154-011-9199-8     Document Type: Review

References (66)

1. Bergwitz C, Juppner H. Regulation of phosphate homeostasis by PTH, vitamin D, and FGF23. Annu Rev Med. 2010;61:91-104.
2. Kolek OI, Hines ER, Jones MD, Lesueur LK, Lipko MA, Kiela PR, et al. 1{alpha},25-Dihydroxyvitamin D3 upregulates FGF23 gene expression in bone: the final link in a renal-gastrointestinal-skeletal axis that controls phosphate transport. Am J Physiol Gastrointest Liver Physiol. 2005;289(6):G1036-42. (Pubitemid 41740608)
3. Saito H, Maeda A, Ohtomo S, Hirata M, Kusano K, Kato S, et al. Circulating FGF-23 is regulated by 1alpha,25-dihydroxyvitamin D3 and phosphorus in vivo. J Biol Chem. 2005;280(4):2543-9. (Pubitemid 40189356)
4. Liu S, Tang W, Zhou J, Stubbs JR, Luo Q, Pi M, et al. Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D. J Am Soc Nephrol. 2006;17(5):1305-15. (Pubitemid 43673410)
5. Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 1997;390(6655):45-51. (Pubitemid 27494749)
6. Kiela PR, Ghishan FK. Recent advances in the renal-skeletal-gut axis that controls phosphate homeostasis. Lab Invest. 2009;89(1):7-14.
7. Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, et al. FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res. 2004;19(3):429-35. (Pubitemid 38787398)
8. Shimada T, Kakitani M, Yamazaki Y, Hasegawa H, Takeuchi Y, Fujita T, et al. Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest. 2004;113(4):561-8. (Pubitemid 38542505)
9. Haussler MR, Haussler CA, Bartik L, Whitfield GK, Hsieh JC, Slater S, et al. Vitamin D receptor: molecular signaling and actions of nutritional ligands in disease prevention. Nutr Rev. 2008;66(10 Suppl 2):S98-S112.
10. Haussler MR, Haussler CA, Whitfield GK, Hsieh JC, Thompson PD, Barthel TK, et al. The nuclear vitamin D receptor controls the expression of genes encoding factors which feed the "Fountain of Youth" to mediate healthful aging. J Steroid Biochem Mol Biol. 2010;121:88-97.
11. Ben-Dov IZ, Galitzer H, Lavi-Moshayoff V, Goetz R, Kuro-o M, Mohammadi M, et al. The parathyroid is a target organ for FGF23 in rats. J Clin Invest. 2007;117(12):4003-8. (Pubitemid 350224109)
12. Razzaque MS. The FGF23-Klotho axis: endocrine regulation of phosphate homeostasis. Nat Rev Endocrinol. 2009;5(11):611-9.
13. Gattineni J, Twombley K, Goetz R, Mohammadi M, Baum M. Regulation of serum 1,25(OH)2Vitamin D3 levels by fibroblast growth factor 23 is mediated by FGF receptors 3 and 4. Am J Physiol Renal Physiol. 2011;301(2):F371-7.
14. Perwad F, Zhang MY, Tenenhouse HS, Portale AA. Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1alpha-hydroxylase expression in vitro. Am J Physiol Renal Physiol. 2007;293(5): F1577-83. (Pubitemid 350085994)
15. Fukuda T, Kanomata K, Nojima J, Urakawa I, Suzawa T, Imada M, et al. FGF23 induces expression of two isoforms of NAB2, which are corepressors of Egr-1. Biochem Biophys Res Commun. 2007;353(1):147-51. (Pubitemid 44958353)
16. Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005;16(2):139-49. (Pubitemid 40616112)
17. Hesse M, Frohlich LF, Zeitz U, Lanske B, Erben RG. Ablation of vitamin D signaling rescues bone, mineral, and glucose homeostasis in Fgf-23 deficient mice. Matrix Biol. 2007;26(2):75-84. (Pubitemid 46187039)
18. Renkema KY, Alexander RT, Bindels RJ, Hoenderop JG. Calcium and phosphate homeostasis: concerted interplay of new regulators. Ann Med. 2008;40(2):82-91. (Pubitemid 351640643)
19. Yuan B, Takaiwa M, Clemens TL, Feng JQ, Kumar R, Rowe PS, et al. Aberrant Phex function in osteoblasts and osteocytes alone underlies murine X-linked hypophosphatemia. J Clin Invest. 2008;118(2):722-34. (Pubitemid 351206560)
20. Fukumoto S. Fibroblast growth factor (FGF) 23 works as a phosphate-regulating hormone and is involved in the pathogenesis of several disorders of phosphate metabolism. Rinsho Byori. 2007;55(6):555-9.
21. Yu X, Sabbagh Y, Davis SI, Demay MB, White KE. Genetic dissection of phosphate- and vitamin D-mediated regulation of circulating Fgf23 concentrations. Bone. 2005;36(6):971-7. (Pubitemid 40797997)
22. Kim TH, Abdullaev ZK, Smith AD, Ching KA, Loukinov DI, Green RD, et al. Analysis of the vertebrate insulator protein CTCF-binding sites in the human genome. Cell. 2007;128(6):1231- 45.
23. Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, et al. High-resolution profiling of histone methylations in the human genome. Cell. 2007;129(4):823-37. (Pubitemid 46802390)
24. Pike JW, Meyer MB, Martowicz ML, Bishop KA, Lee SM, Nerenz RD, et al. Emerging regulatory paradigms for control of gene expression by 1,25-dihydroxyvitamin D(3). J Steroid Biochem Mol Biol. 2010;121:130-5.
25. Masuyama R, Stockmans I, Torrekens S, Van Looveren R, Maes C, Carmeliet P, et al. Vitamin D receptor in chondrocytes promotes osteoclastogenesis and regulates FGF23 production in osteoblasts. J Clin Invest. 2006;116(12):3150-9. (Pubitemid 44878629)
26. Hsieh A, Gurevich M, Mathern D, Kaczmarska MJ, Haussler CA, Whitfield GK, et al. Identification of cEts1 and STAT1 as potential primary targets in the secondary gene regulation of the human fibroblast growth factor-23 gene by 1,25-dihydroxyvitamin D3. J Bone Miner Res. 2007;22:S402.
27. Ito M, Sakai Y, Furumoto M, Segawa H, Haito S, Yamanaka S, et al. Vitamin D and phosphate regulate fibroblast growth factor-23 in K-562 cells. Am J Physiol Endocrinol Metab. 2005;288(6): E1101-9. (Pubitemid 40726796)
28. Juppner H, Wolf M, Salusky IB. FGF-23: more than a regulator of renal phosphate handling? J Bone Miner Res. 2010;25(10):2091-7.
29. Fukumoto S. FGF23: phosphate metabolism and beyond. IBMS BoneKEy. 2010;7(8):268-78.
30. Miedlich SU, Zhu ED, Sabbagh Y, Demay MB. The receptor-dependent actions of 1,25-dihydroxyvitamin D are required for normal growth plate maturation in NPt2a knockout mice. Endocrinology. 2010;151(10):4607-12.
31. Tsuji K, Maeda T, Kawane T, Matsunuma A, Horiuchi N. Leptin stimulates fibroblast growth factor 23 expression in bone and suppresses renal 1alpha,25-dihydroxyvitamin D3 synthesis in leptin-deficient mice. J Bone Miner Res. 2010;25(8):1711-23.
32. Durant L, Watford WT, Ramos HL, Laurence A, Vahedi G, Wei L, et al. Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis. Immunity. 2010;32(5):605-15.
33. Farrow EG, Davis SI, Ward LM, Summers LJ, Bubbear JS, Keen R, et al. Molecular analysis of DMP1 mutants causing autosomal recessive hypophosphatemic rickets. Bone. 2009;44(2):287-94.
34. Martin A, Liu S, David V, Li H, Karydis A, Feng JQ, et al. Bone proteins PHEX and DMP1 regulate fibroblastic growth factor Fgf23 expression in osteocytes through a common pathway involving FGF receptor (FGFR) signaling. FASEB J. 2011;25 (8):2551-62.
35. Ichikawa S, Imel EA, Kreiter ML, Yu X, Mackenzie DS, Sorenson AH, et al. A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis. J Clin Invest. 2007;117(9):2684- 91.
36. Kuro-o M. Klotho. Pflugers Arch. 2010;459(2):333-43.
37. Chen CD, Podvin S, Gillespie E, Leeman SE, Abraham CR. Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17. Proc Natl Acad Sci USA. 2007;104(50):19796-801.
38. Matsumura Y, Aizawa H, Shiraki-Iida T, Nagai R, Kuro-o M, Nabeshima Y. Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein. Biochem Biophys Res Commun. 1998;242(3):626-30. (Pubitemid 28412578)
39. Thurston RD, Larmonier CB, Majewski PM, Ramalingam R, Midura-Kiela M, Laubitz D, et al. Tumor necrosis factor and interferon-gamma down-regulate Klotho in mice with colitis. Gastroenterology. 2010;138(4):1384-94. 94 e1-2.
40. Quarles LD. Endocrine functions of bone in mineral metabolism regulation. J Clin Invest. 2008;118(12):3820-8.
41. Tsujikawa H, Kurotaki Y, Fujimori T, Fukuda K, Nabeshima Y. Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system. Mol Endocrinol. 2003;17(12):2393- 403.
42. Barthel TK, Mathern DR, Whitfield GK, Haussler CA, Hopper IV HA, Hsieh JC, et al. 1,25-Dihydroxyvitamin D3/VDR-mediated induction of FGF23 as well as transcriptional control of other bone anabolic and catabolic genes that orchestrate the regulation of phosphate and calcium mineral metabolism. J Steroid Biochem Mol Biol. 2007;103(3-5):381-8. (Pubitemid 46415670)
43. Bartik L, Whitfield GK, Kaczmarska M, Lowmiller CL, Moffet EW, Furmick JK, et al. Curcumin: a novel nutritionally derived ligand of the vitamin D receptor with implications for colon cancer chemoprevention. J Nutr Biochem. 2010;21:1153-61.
44. Bishop KA, Meyer MB, Pike JW. A novel distal enhancer mediates cytokine induction of mouse RANKl gene expression. Mol Endocrinol. 2009;23(12):2095-110.
45. Keisala T, Minasyan A, Lou YR, Zou J, Kalueff AV, Pyykko I, et al. Premature aging in vitamin D receptor mutant mice. J Steroid Biochem Mol Biol. 2009;115(3-5):91-7.
46. Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP. 1,25- Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest. 2002;110(2):229-38. (Pubitemid 34787360)
47. Nagai R, Saito Y, Ohyama Y, Aizawa H, Suga T, Nakamura T, et al. Endothelial dysfunction in the klotho mouse and downregulation of klotho gene expression in various animal models of vascular and metabolic diseases. Cell Mol Life Sci. 2000;57 (5):738-46. (Pubitemid 30392032)
48. Saito Y, Yamagishi T, Nakamura T, Ohyama Y, Aizawa H, Suga T, et al. Klotho protein protects against endothelial dysfunction. Biochem Biophys Res Commun. 1998;248(2):324-9. (Pubitemid 28386420)
49. Mitani H, Ishizaka N, Aizawa T, Ohno M, Usui S, Suzuki T, et al. In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage. Hypertension. 2002;39(4):838-43. (Pubitemid 34437536)
50. 3. Biochem J. 1999;343(Pt 3):705-12.
51. 3. Identification of a vitamin D-responsive element in the human NAPi-3 gene. J Biol Chem. 1998;273(23):14575-81.
52. Masuda M, Yamamoto H, Kozai M, Tanaka S, Ishiguro M, Takei Y, et al. Regulation of renal sodium-dependent phosphate co-transporter genes (Npt2a and Npt2c) by all-trans-retinoic acid and its receptors. Biochem J. 2010;429(3):583-92.
53. Segawa H, Onitsuka A, Kuwahata M, Hanabusa E, Furutani J, Kaneko I, et al. Type IIc sodium-dependent phosphate transporter regulates calcium metabolism. J Am Soc Nephrol. 2009;20(1):104- 13.
54. Lorenz-Depiereux B, Benet-Pages A, Eckstein G, Tenenbaum- Rakover Y, Wagenstaller J, Tiosano D, et al. Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. Am J Hum Genet. 2006;78(2):193-201. (Pubitemid 43157560)
55. Cha SK, Hu MC, Kurosu H, Kuro-o M, Moe O, Huang CL. Regulation of renal outer medullary potassium channel and renal K(+) excretion by Klotho. Mol Pharmacol. 2009;76(1):38-46.
56. Wu X, Li Y. Role of FGF19 induced FGFR4 activation in the regulation of glucose homeostasis. Aging (Albany NY). 2009;1 (12):1023-7.
57. Kurosu H, Kuro-o M. The Klotho gene family and the endocrine fibroblast growth factors. Curr Opin Nephrol Hypertens. 2008;17 (4):368-72.
58. Shardell M, Hicks GE, Miller RR, Kritchevsky S, Andersen D, Bandinelli S, et al. Association of low vitamin D levels with the frailty syndrome in men and women. J Gerontol A Biol Sci Med Sci. 2009;64(1):69-75.
59. Ensrud KE, Ewing SK, Fredman L, Hochberg MC, Cauley JA, Hillier TA, et al. Circulating 25-hydroxyvitamin D levels and frailty status in older women. J Clin Endocrinol Metab. 2010;95 (12):5266-73.
60. Tuohimaa P, Tenkanen L, AhonenM, Lumme S, Jellum E, Hallmans G, et al. Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case-control study in the Nordic countries. Int J Cancer. 2004;108(1):104-8. (Pubitemid 37444451)
61. Manson JE, Mayne ST, Clinton SK. Vitamin D and prevention of cancer-ready for prime time? New Engl J Med. 2011;364(15):1385- 7.
62. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008;117(4):503-11.
63. Watson KE, Abrolat ML, Malone LL, Hoeg JM, Doherty T, Detrano R, et al. Active serum vitamin D levels are inversely correlated with coronary calcification. Circulation. 1997;96(6):1755-60. (Pubitemid 27400730)
64. Ohnishi M, Razzaque MS. Dietary and genetic evidence for phosphate toxicity accelerating mammalian aging. FASEB J. 2010;24(9):3562-71.
65. Takemura A, Iijima K, Ota H, Son BK, Ito Y, Ogawa S, et al. Sirtuin 1 retards hyperphosphatemia-induced calcification of vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2011;31(9):2054-62.
66. Yoshizawa T, Handa Y, Uematsu Y, Takeda S, Sekine K, Yoshihara Y, et al. Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning. Nat Genet. 1997;16(4):391-6. (Pubitemid 27323308)