Vitamin D Biochemistry and Physiology

  • Daniel D. BikleEmail author
Part of the Contemporary Endocrinology book series (COE)


The vitamin D receptor (VDR) is found in nearly every cell in the body. Moreover, the enzyme, CYP27B1, that produces the active form of the hormone, 1,25-dihydroxyvitamin D (1,25(OH)2D), is also widespread, although perhaps not as ubiquitous as VDR. These observations underlie the recent understanding that vitamin D does much more than regulate bone mineral metabolism through its actions on intestinal calcium and phosphate absorption, renal calcium and phosphate reabsorption, and bone development and remodeling. In this chapter, I will review the production of vitamin D in the skin, its subsequent metabolism to the major circulating metabolite 25-hydroxyvitamin D (25(OH)D) by the different 25-hydroxylases in the liver and elsewhere, and the metabolism of 25(OH)D to 1,25(OH)2D in the kidney and elsewhere. This last step is tightly regulated, but its regulation differs according to the cell involved. Transport of the vitamin D metabolites in blood by the vitamin D-binding protein (DBP) and albumin and its uptake by different tissues are then discussed emphasizing that some cells rely on diffusion of the metabolites across the membrane in free form, whereas others have a mechanism to take up the metabolite bound to DBP. The molecular mechanism of action of 1,25(OH)2D will then be reviewed, describing the very large number of cellular processes regulated by 1,25(OH)2D, emphasizing the cell specificity of this regulation. In the final section, I will provide examples of different physiologic functions of vitamin D signaling in its regulation of proliferation/differentiation, hormone regulation, and immune function.


Vitamin D Vitamin D receptor CYP27B1 Calcitriol Calcium Vitamin D-binding protein Genomic regulation Cancer Immunity Hormone regulation Proliferation Differentiation 


  1. 1.
    Holick MF, McLaughlin JA, Clark MB, Holick SA, PJ JT, Anderson RR, et al. Photosynthesis of previtamin D3 in human and the physiologic consequences. Science. 1980;210:203–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Webb AR, DeCosta BR, Holick MF. Sunlight regulates the cutaneous production of vitamin D3 by causing its photodegradation. J Clin Endocrinol Metab. 1989;68(5):882–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Houghton LA, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr. 2006;84(4):694–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Hollis BW. Comparison of equilibrium and disequilibrium assay conditions for ergocalciferol, cholecalciferol and their major metabolites. J Steroid Biochem. 1984;21(1):81–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Horst RL, Reinhardt TA, Ramberg CF, Koszewski NJ, Napoli JL. 24-Hydroxylation of 1,25-dihydroxyergocalciferol. An unambiguous deactivation process. J Biol Chem. 1986;261(20):9250–6.PubMedGoogle Scholar
  6. 6.
    Tripkovic L, Lambert H, Hart K, Smith CP, Bucca G, Penson S, et al. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. Am J Clin Nutr. 2012;95(6):1357–64.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Sugimoto H, Shiro Y. Diversity and substrate specificity in the structures of steroidogenic cytochrome P450 enzymes. Biol Pharm Bull. 2012;35(6):818–23.PubMedCrossRefGoogle Scholar
  8. 8.
    Zhu JG, Ochalek JT, Kaufmann M, Jones G, Deluca HF. CYP2R1 is a major, but not exclusive, contributor to 25-hydroxyvitamin D production in vivo. Proc Natl Acad Sci U S A. 2013;110(39):15650–5.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Moghadasian MH. Cerebrotendinous xanthomatosis: clinical course, genotypes and metabolic backgrounds. Clin Invest Med. 2004;27(1):42–50.PubMedGoogle Scholar
  10. 10.
    Cheng JB, Motola DL, Mangelsdorf DJ, Russell DW. De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase. J Biol Chem. 2003;278(39):38084–93.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Cheng JB, Levine MA, Bell NH, Mangelsdorf DJ, Russell DW. Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc Natl Acad Sci U S A. 2004;101(20):7711–5.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Gupta RP, Hollis BW, Patel SB, Patrick KS, Bell NH. CYP3A4 is a human microsomal vitamin D 25-hydroxylase. J Bone Miner Res. 2004;19(4):680–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Fu GK, Lin D, Zhang MY, Bikle DD, Shackleton CH, Miller WL, et al. Cloning of human 25-hydroxyvitamin D-1 alpha-hydroxylase and mutations causing vitamin D-dependent rickets type 1. Mol Endocrinol (Baltimore, Md). 1997;11(13):1961–70.Google Scholar
  14. 14.
    Shinki T, Shimada H, Wakino S, Anazawa H, Hayashi M, Saruta T, et al. Cloning and expression of rat 25-hydroxyvitamin D3-1alpha-hydroxylase cDNA. Proc Natl Acad Sci U S A. 1997;94(24):12920–5.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Takeyama K, Kitanaka S, Sato T, Kobori M, Yanagisawa J, Kato S. 25-Hydroxyvitamin D3 1alpha-hydroxylase and vitamin D synthesis. Science. 1997;277(5333):1827–30.PubMedCrossRefGoogle Scholar
  16. 16.
    St-Arnaud R, Messerlian S, Moir JM, Omdahl JL, Glorieux FH. The 25-hydroxyvitamin D 1-alpha-hydroxylase gene maps to the pseudovitamin D-deficiency rickets (PDDR) disease locus. J Bone Miner Res. 1997;12(10):1552–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Bikle D. Extra renal synthesis of 1,25-dihydroxyvitamin D and its health implications. In: Holick M, editor. Vitamin D: physiology, molecular biology, and clinical applications. New York: Humana Press; 2010. p. 277–95.CrossRefGoogle Scholar
  18. 18.
    Bikle DD, Rasmussen H. The ionic control of 1,25-dihydroxyvitamin D3 production in isolated chick renal tubules. J Clin Invest. 1975;55(2):292–8.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Bikle DD, Murphy EW, Rasmussen H. The ionic control of 1,25-dihydroxyvitamin D3 synthesis in isolated chick renal mitochondria. The role of calcium as influenced by inorganic phosphate and hydrogen-ion. J Clin Invest. 1975;55(2):299–304.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Kim MS, Fujiki R, Kitagawa H, Kato S. 1alpha,25(OH)2D3-induced DNA methylation suppresses the human CYP27B1 gene. Mol Cell Endocrinol. 2007;265–266:168–73.PubMedCrossRefGoogle Scholar
  21. 21.
    Adams JS, Gacad MA. Characterization of 1 alpha-hydroxylation of vitamin D3 sterols by cultured alveolar macrophages from patients with sarcoidosis. J Exp Med. 1985;161(4):755–65.PubMedCrossRefGoogle Scholar
  22. 22.
    Ren S, Nguyen L, Wu S, Encinas C, Adams JS, Hewison M. Alternative splicing of vitamin D-24-hydroxylase: a novel mechanism for the regulation of extrarenal 1,25-dihydroxyvitamin D synthesis. J Biol Chem. 2005;280(21):20604–11.PubMedCrossRefGoogle Scholar
  23. 23.
    Bikle DD, Pillai S, Gee E, Hincenbergs M. Tumor necrosis factor-alpha regulation of 1,25-dihydroxyvitamin D production by human keratinocytes. Endocrinology. 1991;129(1):33–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Bikle DD, Pillai S, Gee E, Hincenbergs M. Regulation of 1,25-dihydroxyvitamin D production in human keratinocytes by interferon-gamma. Endocrinology. 1989;124(2):655–60.PubMedCrossRefGoogle Scholar
  25. 25.
    Pryke AM, Duggan C, White CP, Posen S, Mason RS. Tumor necrosis factor-alpha induces vitamin D-1-hydroxylase activity in normal human alveolar macrophages. J Cell Physiol. 1990;142(3):652–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Gyetko MR, Hsu CH, Wilkinson CC, Patel S, Young E. Monocyte 1 alpha-hydroxylase regulation: induction by inflammatory cytokines and suppression by dexamethasone and uremia toxin. J Leukoc Biol. 1993;54(1):17–22.PubMedCrossRefGoogle Scholar
  27. 27.
    Stoffels K, Overbergh L, Giulietti A, Verlinden L, Bouillon R, Mathieu C. Immune regulation of 25-hydroxyvitamin-D3-1alpha-hydroxylase in human monocytes. J Bone Miner Res. 2006;21(1):37–47.PubMedCrossRefGoogle Scholar
  28. 28.
    Bacchetta J, Sea JL, Chun RF, Lisse TS, Wesseling-Perry K, Gales B, et al. Fibroblast growth factor 23 inhibits extrarenal synthesis of 1,25-dihydroxyvitamin D in human monocytes. J Bone Miner Res. 2013;28(1):46–55.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Krajisnik T, Bjorklund P, Marsell R, Ljunggren O, Akerstrom G, Jonsson KB, et al. Fibroblast growth factor-23 regulates parathyroid hormone and 1alpha-hydroxylase expression in cultured bovine parathyroid cells. J Endocrinol. 2007;195(1):125–31.PubMedCrossRefGoogle Scholar
  30. 30.
    Jones G, Prosser DE, Kaufmann M. 25-Hydroxyvitamin D-24-hydroxylase (CYP24A1): its important role in the degradation of vitamin D. Arch Biochem Biophys. 2012;523(1):9–18.PubMedCrossRefGoogle Scholar
  31. 31.
    Sakaki T, Sawada N, Komai K, Shiozawa S, Yamada S, Yamamoto K, et al. Dual metabolic pathway of 25-hydroxyvitamin D3 catalyzed by human CYP24. Eur J Biochem. 2000;267(20):6158–65.PubMedCrossRefGoogle Scholar
  32. 32.
    Prosser DE, Kaufmann M, O’Leary B, Byford V, Jones G. Single A326G mutation converts human CYP24A1 from 25-OH-D3-24-hydroxylase into -23-hydroxylase, generating 1alpha,25-(OH)2D3-26,23-lactone. Proc Natl Acad Sci U S A. 2007;104(31):12673–8.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Plachot JJ, Du Bois MB, Halpern S, Cournot-Witmer G, Garabedian M, Balsan S. In vitro action of 1,25-dihydroxycholecalciferol and 24,25-dihydroxycholecalciferol on matrix organization and mineral distribution in rabbit growth plate. Metab Bone Dis Relat Res. 1982;4(2):135–42.PubMedCrossRefGoogle Scholar
  34. 34.
    St-Arnaud R, Arabian A, Travers R, Barletta F, Raval-Pandya M, Chapin K, et al. Deficient mineralization of intramembranous bone in vitamin D-24-hydroxylase-ablated mice is due to elevated 1,25-dihydroxyvitamin D and not to the absence of 24,25-dihydroxyvitamin D. Endocrinology. 2000;141(7):2658–66.PubMedCrossRefGoogle Scholar
  35. 35.
    Schlingmann KP, Kaufmann M, Weber S, Irwin A, Goos C, John U, et al. Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N Engl J Med. 2011;365(5):410–21.PubMedCrossRefGoogle Scholar
  36. 36.
    Zierold C, Darwish HM, DeLuca HF. Two vitamin D response elements function in the rat 1,25-dihydroxyvitamin D 24-hydroxylase promoter. J Biol Chem. 1995;270(4):1675–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Meyer MB, Goetsch PD, Pike JW. A downstream intergenic cluster of regulatory enhancers contributes to the induction of CYP24A1 expression by 1alpha,25-dihydroxyvitamin D3. J Biol Chem. 2010;285(20):15599–610.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Zierold C, Reinholz GG, Mings JA, Prahl JM, DeLuca HF. Regulation of the procine 1,25-dihydroxyvitamin D3-24-hydroxylase (CYP24) by 1,25-dihydroxyvitamin D3 and parathyroid hormone in AOK-B50 cells. Arch Biochem Biophys. 2000;381(2):323–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Zierold C, Mings JA, DeLuca HF. Parathyroid hormone regulates 25-hydroxyvitamin D(3)-24-hydroxylase mRNA by altering its stability. Proc Natl Acad Sci U S A. 2001;98(24):13572–6.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Perwad F, Azam N, Zhang MY, Yamashita T, Tenenhouse HS, Portale AA. Dietary and serum phosphorus regulate fibroblast growth factor 23 expression and 1,25-dihydroxyvitamin D metabolism in mice. Endocrinology. 2005;146(12):5358–64.PubMedCrossRefGoogle Scholar
  41. 41.
    Ohata Y, Yamazaki M, Kawai M, Tsugawa N, Tachikawa K, Koinuma T, et al. Elevated fibroblast growth factor 23 exerts its effects on placenta and regulates vitamin D metabolism in pregnancy of Hyp mice. J Bone Miner Res. 2014;29(7):1627–38.PubMedCrossRefGoogle Scholar
  42. 42.
    Armbrecht HJ, Hodam TL, Boltz MA, Partridge NC, Brown AJ, Kumar VB. Induction of the vitamin D 24-hydroxylase (CYP24) by 1,25-dihydroxyvitamin D3 is regulated by parathyroid hormone in UMR106 osteoblastic cells. Endocrinology. 1998;139(8):3375–81.PubMedCrossRefGoogle Scholar
  43. 43.
    Bailey D, Veljkovic K, Yazdanpanah M, Adeli K. Analytical measurement and clinical relevance of vitamin D(3) C3-epimer. Clin Biochem. 2013;46(3):190–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Reddy GS, Muralidharan KR, Okamura WH, Tserng KY, McLane JA. Metabolism of 1alpha,25-dihydroxyvitamin D(3) and its C-3 epimer 1alpha,25-dihydroxy-3-epi-vitamin D(3) in neonatal human keratinocytes. Steroids. 2001;66(3–5):441–50.PubMedCrossRefGoogle Scholar
  45. 45.
    Kamao M, Tatematsu S, Hatakeyama S, Sakaki T, Sawada N, Inouye K, et al. C-3 epimerization of vitamin D3 metabolites and further metabolism of C-3 epimers: 25-hydroxyvitamin D3 is metabolized to 3-epi-25-hydroxyvitamin D3 and subsequently metabolized through C-1alpha or C-24 hydroxylation. J Biol Chem. 2004;279(16):15897–907.PubMedCrossRefGoogle Scholar
  46. 46.
    Brown AJ, Ritter C, Slatopolsky E, Muralidharan KR, Okamura WH, Reddy GS. 1Alpha,25-dihydroxy-3-epi-vitamin D3, a natural metabolite of 1alpha,25-dihydroxyvitamin D3, is a potent suppressor of parathyroid hormone secretion. J Cell Biochem. 1999;73(1):106–13.PubMedCrossRefGoogle Scholar
  47. 47.
    Slominski AT, Janjetovic Z, Fuller BE, Zmijewski MA, Tuckey RC, Nguyen MN, et al. Products of vitamin D3 or 7-dehydrocholesterol metabolism by cytochrome P450scc show anti-leukemia effects, having low or absent calcemic activity. PLoS One. 2010;5(3):e9907.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Cooke NE, Haddad JG. Vitamin D binding protein (Gc-globulin). Endocr Rev. 1989;10(3):294–307.PubMedCrossRefGoogle Scholar
  49. 49.
    Bikle DD, Gee E, Halloran B, Haddad JG. Free 1,25-dihydroxyvitamin D levels in serum from normal subjects, pregnant subjects, and subjects with liver disease. J Clin Invest. 1984;74(6):1966–71.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Bikle DD, Siiteri PK, Ryzen E, Haddad JG. Serum protein binding of 1,25-dihydroxyvitamin D: a reevaluation by direct measurement of free metabolite levels. J Clin Endocrinol Metab. 1985;61(5):969–75.PubMedCrossRefGoogle Scholar
  51. 51.
    Bikle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, Haddad JG. Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab. 1986;63(4):954–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Bikle DD, Halloran BP, Gee E, Ryzen E, Haddad JG. Free 25-hydroxyvitamin D levels are normal in subjects with liver disease and reduced total 25-hydroxyvitamin D levels. J Clin Invest. 1986;78(3):748–52.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Aggarwal A, Yadav AK, Ramachandran R, Kumar V, Kumar V, Sachdeva N, et al. Bioavailable vitamin D levels are reduced and correlate with bone mineral density and markers of mineral metabolism in adults with nephrotic syndrome. Nephrology (Carlton). 2016;21(6):483–9.CrossRefGoogle Scholar
  54. 54.
    Kim HJ, Ji M, Song J, Moon HW, Hur M, Yun YM. Clinical utility of measurement of vitamin D-binding protein and calculation of bioavailable vitamin D in assessment of vitamin D status. Ann Lab Med. 2017;37(1):34–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Lai JC, Bikle DD, Lizaola B, Hayssen H, Terrault NA, Schwartz JB. Total 25(OH) vitamin D, free 25(OH) vitamin D and markers of bone turnover in cirrhotics with and without synthetic dysfunction. Liver Int. 2015;35(10):2294–300.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Schwartz JB, Lai J, Lizaola B, Kane L, Markova S, Weyland P, et al. A comparison of measured and calculated free 25(OH) vitamin D levels in clinical populations. J Clin Endocrinol Metab. 2014;99(5):1631–7.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Pettifor JM, Bikle DD, Cavaleros M, Zachen D, Kamdar MC, Ross FP. Serum levels of free 1,25-dihydroxyvitamin D in vitamin D toxicity. Ann Intern Med. 1995;122(7):511–3.PubMedCrossRefGoogle Scholar
  58. 58.
    Cooke NE, David EV. Serum vitamin D-binding protein is a third member of the albumin and alpha fetoprotein gene family. J Clin Invest. 1985;76(6):2420–4.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Recant L, Riggs DS. Thyroid function in nephrosis. J Clin Invest. 1952;31(8):789–97.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Bouillon R, Van Assche FA, Van Baelen H, Heyns W, De Moor P. Influence of the vitamin D-binding protein on the serum concentration of 1,25-dihydroxyvitamin D3. Significance of the free 1,25-dihydroxyvitamin D3 concentration. J Clin Invest. 1981;67(3):589–96.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Safadi FF, Thornton P, Magiera H, Hollis BW, Gentile M, Haddad JG, et al. Osteopathy and resistance to vitamin D toxicity in mice null for vitamin D binding protein. J Clin Invest. 1999;103(2):239–51.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Nykjaer A, Dragun D, Walther D, Vorum H, Jacobsen C, Herz J, et al. An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. Cell. 1999;96(4):507–15.PubMedCrossRefGoogle Scholar
  63. 63.
    Nykjaer A, Fyfe JC, Kozyraki R, Leheste JR, Jacobsen C, Nielsen MS, et al. Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3). Proc Natl Acad Sci U S A. 2001;98(24):13895–900.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Lundgren S, Carling T, Hjalm G, Juhlin C, Rastad J, Pihlgren U, et al. Tissue distribution of human gp330/megalin, a putative Ca(2+)-sensing protein. J Histochem Cytochem. 1997;45(3):383–92.PubMedCrossRefGoogle Scholar
  65. 65.
    Uitterlinden AG, Arp PP, Paeper BW, Charmley P, Proll S, Rivadeneira F, et al. Polymorphisms in the sclerosteosis/van Buchem disease gene (SOST) region are associated with bone-mineral density in elderly whites. Am J Hum Genet. 2004;75(6):1032–45.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Rochel N, Wurtz JM, Mitschler A, Klaholz B, Moras D. The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand. Mol Cell. 2000;5(1):173–9.PubMedCrossRefGoogle Scholar
  67. 67.
    Carlson M, Laurent BC. The SNF/SWI family of global transcriptional activators. Curr Opin Cell Biol. 1994;6(3):396–402.PubMedCrossRefGoogle Scholar
  68. 68.
    Smith CL, O’Malley BW. Coregulator function: a key to understanding tissue specificity of selective receptor modulators. Endocr Rev. 2004;25(1):45–71.PubMedCrossRefGoogle Scholar
  69. 69.
    Rachez C, Freedman LP. Mechanisms of gene regulation by vitamin D(3) receptor: a network of coactivator interactions. Gene. 2000;246(1–2):9–21.PubMedCrossRefGoogle Scholar
  70. 70.
    Wang Z, Gerstein M, Snyder M. RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet. 2009;10(1):57–63.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Kellis M, Wold B, Snyder MP, Bernstein BE, Kundaje A, Marinov GK, et al. Defining functional DNA elements in the human genome. Proc Natl Acad Sci U S A. 2014;111(17):6131–8.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, et al. Multiplex genome engineering using CRISPR/Cas systems. Science. 2013;339(6121):819–23.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Meyer MB, Goetsch PD, Pike JW. Genome-wide analysis of the VDR/RXR cistrome in osteoblast cells provides new mechanistic insight into the actions of the vitamin D hormone. J Steroid Biochem Mol Biol. 2010;121(1–2):136–41.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Ramagopalan SV, Heger A, Berlanga AJ, Maugeri NJ, Lincoln MR, Burrell A, et al. A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome Res. 2010;20(10):1352–60.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Carlberg C, Seuter S, Heikkinen S. The first genome-wide view of vitamin D receptor locations and their mechanistic implications. Anticancer Res. 2012;32(1):271–82.PubMedGoogle Scholar
  76. 76.
    Zella LA, Meyer MB, Nerenz RD, Lee SM, Martowicz ML, Pike JW. Multifunctional enhancers regulate mouse and human vitamin D receptor gene transcription. Mol Endocrinol (Baltimore, Md). 2010;24(1):128–47.CrossRefGoogle Scholar
  77. 77.
    Meyer MB, Goetsch PD, Pike JW. VDR/RXR and TCF4/beta-catenin cistromes in colonic cells of colorectal tumor origin: impact on c-FOS and c-MYC gene expression. Mol Endocrinol (Baltimore, Md). 2012;26(1):37–51.CrossRefGoogle Scholar
  78. 78.
    Ernst J, Kheradpour P, Mikkelsen TS, Shoresh N, Ward LD, Epstein CB, et al. Mapping and analysis of chromatin state dynamics in nine human cell types. Nature. 2011;473(7345):43–9.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Kim S, Yamazaki M, Zella LA, Shevde NK, Pike JW. Activation of receptor activator of NF-kappaB ligand gene expression by 1,25-dihydroxyvitamin D3 is mediated through multiple long-range enhancers. Mol Cell Biol. 2006;26(17):6469–86.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Galli C, Zella LA, Fretz JA, Fu Q, Pike JW, Weinstein RS, et al. Targeted deletion of a distant transcriptional enhancer of the receptor activator of nuclear factor-kappaB ligand gene reduces bone remodeling and increases bone mass. Endocrinology. 2008;149(1):146–53.PubMedCrossRefGoogle Scholar
  81. 81.
    Onal M, St John HC, Danielson AL, Markert JW, Riley EM, Pike JW. Unique distal enhancers linked to the mouse Tnfsf11 gene direct tissue-specific and inflammation-induced expression of RANKL. Endocrinology. 2016;157(2):482–96.PubMedCrossRefGoogle Scholar
  82. 82.
    Norman AW, Okamura WH, Hammond MW, Bishop JE, Dormanen MC, Bouillon R, et al. Comparison of 6-s-cis- and 6-s-trans-locked analogs of 1alpha,25-dihydroxyvitamin D3 indicates that the 6-s-cis conformation is preferred for rapid nongenomic biological responses and that neither 6-s-cis- nor 6-s-trans-locked analogs are preferred for genomic biological responses. Mol Endocrinol (Baltimore, Md). 1997;11(10):1518–31.Google Scholar
  83. 83.
    Schwartz N, Verma A, Bivens CB, Schwartz Z, Boyan BD. Rapid steroid hormone actions via membrane receptors. Biochim Biophys Acta. 2016;1863(9):2289–98.PubMedCrossRefGoogle Scholar
  84. 84.
    Sequeira VB, Rybchyn MS, Tongkao-On W, Gordon-Thomson C, Malloy PJ, Nemere I, et al. The role of the vitamin D receptor and ERp57 in photoprotection by 1alpha,25-dihydroxyvitamin D3. Mol Endocrinol. 2012;26(4):574–82.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Mizwicki MT, Norman AW. The vitamin D sterol-vitamin D receptor ensemble model offers unique insights into both genomic and rapid-response signaling. Sci Signal. 2009;2(75):re4.PubMedCrossRefGoogle Scholar
  86. 86.
    Nemere I, Farach-Carson MC, Rohe B, Sterling TM, Norman AW, Boyan BD, et al. Ribozyme knockdown functionally links a 1,25(OH)2D3 membrane binding protein (1,25D3-MARRS) and phosphate uptake in intestinal cells. Proc Natl Acad Sci U S A. 2004;101(19):7392–7.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Huhtakangas JA, Olivera CJ, Bishop JE, Zanello LP, Norman AW. The vitamin D receptor is present in caveolae-enriched plasma membranes and binds 1 alpha,25(OH)2-vitamin D3 in vivo and in vitro. Mol Endocrinol (Baltimore, Md). 2004;18(11):2660–71.CrossRefGoogle Scholar
  88. 88.
    Nemere I, Garbi N, Hammerling GJ, Khanal RC. Intestinal cell calcium uptake and the targeted knockout of the 1,25D3-MARRS (membrane-associated, rapid response steroid-binding) receptor/PDIA3/Erp57. J Biol Chem. 2010;285(41):31859–66.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Chen J, Olivares-Navarrete R, Wang Y, Herman TR, Boyan BD, Schwartz Z. Protein-disulfide isomerase-associated 3 (Pdia3) mediates the membrane response to 1,25-dihydroxyvitamin D3 in osteoblasts. J Biol Chem. 2010;285(47):37041–50.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Wang Y, Chen J, Lee CS, Nizkorodov A, Riemenschneider K, Martin D, et al. Disruption of Pdia3 gene results in bone abnormality and affects 1alpha,25-dihydroxy-vitamin D3-induced rapid activation of PKC. J Steroid Biochem Mol Biol. 2010;121(1–2):257–60.PubMedCrossRefGoogle Scholar
  91. 91.
    Christakos S, Dhawan P, Porta A, Mady LJ, Seth T. Vitamin D and intestinal calcium absorption. Mol Cell Endocrinol. 2011;347(1–2):25–9.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Bikle DD, Morrissey RL, Zolock DT, Rasmussen H. The intestinal response to vitamin D. Rev Physiol Biochem Pharmacol. 1981;89:63–142.PubMedCrossRefGoogle Scholar
  93. 93.
    Bikle DD, Shoback DM, Munson S. 1,25-dihydroxyvitamin D increases the intracellular free calcium concentration of duodenal epithelial cells. In: Schaefer K, Grigoleit HG, Herrath DV, editors. Vitamin D: chemical, biochemical and clinical update. New York: Walter de Gruyter; 1985. 416 p.Google Scholar
  94. 94.
    Morrissey RL, Zolock DT, Mellick PW, Bikle DD. Influence of cycloheximide and 1,25-dihydroxyvitamin D3 on mitochondrial and vesicle mineralization in the intestine. Cell Calcium. 1980;1:69–79.CrossRefGoogle Scholar
  95. 95.
    Davis WL, Hagler HK, Jones RG, Farmer GR, Cooper OJ, Martin JH, et al. Cryofixation, ultracryomicrotomy, and X-ray microanalysis of enterocytes from chick duodenum: vitamin-D-induced formation of an apical tubulovesicular system. Anat Rec. 1991;229(2):227–39.PubMedCrossRefGoogle Scholar
  96. 96.
    Nemere I, Leathers V, Norman AW. 1,25-Dihydroxyvitamin D3-mediated intestinal calcium transport. Biochemical identification of lysosomes containing calcium and calcium- binding protein (calbindin-D28K). J Biol Chem. 1986;261(34):16106–14.PubMedGoogle Scholar
  97. 97.
    Max EE, Goodman DB, Rasmussen H. Purification and characterization of chick intestine brush border membrane. Effects of 1alpha(OH) vitamin D3 treatment. Biochim Biophys Acta. 1978;511(2):224–39.PubMedCrossRefGoogle Scholar
  98. 98.
    Brasitus TA, Dudeja PK, Eby B, Lau K. Correction by 1,25(OH)2D3 of the abnormal fluidity and lipid composition of enterocyte brush border membranes in vitamin D-deprived rats. J Biol Chem. 1981;256:3354–60.Google Scholar
  99. 99.
    Matsumoto T, Fontaine O, Rasmussen H. Effect of 1,25-dihydroxyvitamin D3 on phospholipid metabolism in chick duodenal mucosal cell. Relationship to its mechanism of action. J Biol Chem. 1981;256(7):3354–60.PubMedGoogle Scholar
  100. 100.
    Hoenderop JG, van der Kemp AW, Hartog A, van de Graaf SF, van Os CH, Willems PH, et al. Molecular identification of the apical Ca2+ channel in 1, 25-dihydroxyvitamin D3-responsive epithelia. J Biol Chem. 1999;274(13):8375–8.PubMedCrossRefGoogle Scholar
  101. 101.
    Peng JB, Chen XZ, Berger UV, Vassilev PM, Brown EM, Hediger MA. A rat kidney-specific calcium transporter in the distal nephron. J Biol Chem. 2000;275(36):28186–94.PubMedGoogle Scholar
  102. 102.
    Bianco SD, Peng JB, Takanaga H, Suzuki Y, Crescenzi A, Kos CH, et al. Marked disturbance of calcium homeostasis in mice with targeted disruption of the Trpv6 calcium channel gene. J Bone Miner Res. 2007;22(2):274–85.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Kutuzova GD, Sundersingh F, Vaughan J, Tadi BP, Ansay SE, Christakos S, et al. TRPV6 is not required for 1alpha,25-dihydroxyvitamin D3-induced intestinal calcium absorption in vivo. Proc Natl Acad Sci U S A. 2008;105(50):19655–9.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Glenney JR Jr, Glenney P. Comparison of Ca++-regulated events in the intestinal brush border. J Cell Biol. 1985;100(3):754–63.PubMedCrossRefGoogle Scholar
  105. 105.
    Bikle DD, Gee E. Free, and not total, 1,25-dihydroxyvitamin D regulates 25-hydroxyvitamin D metabolism by keratinocytes. Endocrinology. 1989;124(2):649–54.PubMedCrossRefGoogle Scholar
  106. 106.
    Bikle DD, Munson S, Chafouleas J. Calmodulin may mediate 1,25-dihydroxyvitamin D-stimulated intestinal calcium transport. FEBS Lett. 1984;174(1):30–3.PubMedCrossRefGoogle Scholar
  107. 107.
    Lambers TT, Weidema AF, Nilius B, Hoenderop JG, Bindels RJ. Regulation of the mouse epithelial Ca2(+) channel TRPV6 by the Ca(2+)-sensor calmodulin. J Biol Chem. 2004;279(28):28855–61.PubMedCrossRefGoogle Scholar
  108. 108.
    Bikle DD, Munson S. The villus gradient of brush border membrane calmodulin and the calcium-independent calmodulin-binding protein parallels that of calcium-accumulating ability. Endocrinology. 1986;118(2):727–32.PubMedCrossRefGoogle Scholar
  109. 109.
    Sampson HW, Matthews JL, Martin JH, Kunin AS. An electron microscopic localization of calcium in the small intestine of normal, rachitic, and vitamin-D-treated rats. Calcif Tissue Res. 1970;5(4):305–16.PubMedCrossRefGoogle Scholar
  110. 110.
    Schaefer HJ. Ultrastructure and ion distribution of the intestinal cell during experimental vitamin D deficiency rickets in rats. Virchows Arch. 1973;359:111–23.CrossRefGoogle Scholar
  111. 111.
    Wasserman RH, Taylor AN. Vitamin D-dependent calcium-binding protein. Response to some physiological and nutritional variables. J Biol Chem. 1968;243(14):3987–93.PubMedGoogle Scholar
  112. 112.
    Lee GS, Lee KY, Choi KC, Ryu YH, Paik SG, Oh GT, et al. Phenotype of a calbindin-D9k gene knockout is compensated for by the induction of other calcium transporter genes in a mouse model. J Bone Miner Res. 2007;22(12):1968–78.PubMedCrossRefGoogle Scholar
  113. 113.
    Benn BS, Ajibade D, Porta A, Dhawan P, Hediger M, Peng JB, et al. Active intestinal calcium transport in the absence of transient receptor potential vanilloid type 6 and calbindin-D9k. Endocrinology. 2008;149(6):3196–205.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Ghijsen WE, De Jong MD, Van Os CH. ATP-dependent calcium transport and its correlation with Ca2+-ATPase activity in basolateral plasma membranes of rat duodenum. Biochim Biophys Acta. 1982;689(2):327–36.PubMedCrossRefGoogle Scholar
  115. 115.
    Cai Q, Chandler JS, Wasserman RH, Kumar R, Penniston JT. Vitamin D and adaptation to dietary calcium and phosphate deficiencies increase intestinal plasma membrane calcium pump gene expression. Proc Natl Acad Sci U S A. 1993;90(4):1345–9.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Wasserman RH, Chandler JS, Meyer SA, Smith CA, Brindak ME, Fullmer CS, et al. Intestinal calcium transport and calcium extrusion processes at the basolateral membrane. J Nutr. 1992;122(3 Suppl):662–71.PubMedCrossRefGoogle Scholar
  117. 117.
    Hoenderop JG, Nilius B, Bindels RJ. Calcium absorption across epithelia. Physiol Rev. 2005;85(1):373–422.PubMedCrossRefGoogle Scholar
  118. 118.
    Xu H, Bai L, Collins JF, Ghishan FK. Molecular cloning, functional characterization, tissue distribution, and chromosomal localization of a human, small intestinal sodium-phosphate (Na+-Pi) transporter (SLC34A2). Genomics. 1999;62(2):281–4.PubMedCrossRefGoogle Scholar
  119. 119.
    Xu H, Bai L, Collins JF, Ghishan FK. Age-dependent regulation of rat intestinal type IIb sodium-phosphate cotransporter by 1,25-(OH)(2) vitamin D(3). Am J Physiol Cell Physiol. 2002;282(3):C487–93.PubMedCrossRefGoogle Scholar
  120. 120.
    Candeal E, Caldas YA, Guillen N, Levi M, Sorribas V. Intestinal phosphate absorption is mediated by multiple transport systems in rats. Am J Physiol Gastrointest Liver Physiol. 2017;312(4):G355–66.PubMedCrossRefGoogle Scholar
  121. 121.
    Fuchs R, Peterlik M. Vitamin D-induced transepithelial phosphate and calcium transport by chick jejunum. Effect of microfilamentous and microtubular inhibitors. FEBS Lett. 1979;100(2):357–9.PubMedCrossRefGoogle Scholar
  122. 122.
    Narbaitz R, Stumpf WE, Sar M, Huang S, DeLuca HF. Autoradiographic localization of target cells for 1 alpha, 25-dihydroxyvitamin D3 in bones from fetal rats. Calcif Tissue Int. 1983;35(2):177–82.PubMedCrossRefGoogle Scholar
  123. 123.
    Boivin G, Mesguich P, Pike JW, Bouillon R, Meunier PJ, Haussler MR, et al. Ultrastructural immunocytochemical localization of endogenous 1,25-dihydroxyvitamin D3 and its receptors in osteoblasts and osteocytes from neonatal mouse and rat calvaria. Bone Miner. 1987;3(2):125–36.PubMedGoogle Scholar
  124. 124.
    Johnson JA, Grande JP, Roche PC, Kumar R. Ontogeny of the 1,25-dihydroxyvitamin D3 receptor in fetal rat bone. J Bone Miner Res. 1996;11(1):56–61.PubMedCrossRefGoogle Scholar
  125. 125.
    Miller SC, Halloran BP, DeLuca HF, Lee WSS. Studies on the role of vitamin D in early skeletal development, mineralization, and growth in rats. Calcif Tissue Int. 1983;35:455–60.PubMedCrossRefGoogle Scholar
  126. 126.
    Li YC, Pirro AE, Amling M, Delling G, Baron R, Bronson R, et al. Targeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopecia. Proc Natl Acad Sci U S A. 1997;94(18):9831–5.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Balsan S, Garabedian M, Larchet M, Gorski AM, Cournot G, Tau C, et al. Long-term nocturnal calcium infusions can cure rickets and promote normal mineralization in hereditary resistance to 1,25-dihydroxyvitamin D. J Clin Invest. 1986;77(5):1661–7.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Li YC, Amling M, Pirro AE, Priemel M, Meuse J, Baron R, et al. Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice. Endocrinology. 1998;139(10):4391–6.PubMedCrossRefGoogle Scholar
  129. 129.
    Xue Y, Fleet JC. Intestinal vitamin D receptor is required for normal calcium and bone metabolism in mice. Gastroenterology. 2009;136(4):1317–27, e1–2.PubMedCrossRefGoogle Scholar
  130. 130.
    Panda DK, Miao D, Bolivar I, Li J, Huo R, Hendy GN, et al. Inactivation of the 25-hydroxyvitamin D 1alpha-hydroxylase and vitamin D receptor demonstrates independent and interdependent effects of calcium and vitamin D on skeletal and mineral homeostasis. J Biol Chem. 2004;279(16):16754–66.PubMedCrossRefGoogle Scholar
  131. 131.
    Sato T, Ono T, Tuan RS. 1,25-Dihydroxy vitamin D3 stimulation of TGF-beta expression in chick embryonic calvarial bone. Differentiation. 1993;52(2):139–50.PubMedCrossRefGoogle Scholar
  132. 132.
    Wang DS, Yamazaki K, Nohtomi K, Shizume K, Ohsumi K, Shibuya M, et al. Increase of vascular endothelial growth factor mRNA expression by 1,25-dihydroxyvitamin D3 in human osteoblast-like cells. J Bone Miner Res. 1996;11(4):472–9.PubMedCrossRefGoogle Scholar
  133. 133.
    Kyeyune-Nyombi E, Lau KH, Baylink DJ, Strong DD. 1,25-Dihydroxyvitamin D3 stimulates both alkaline phosphatase gene transcription and mRNA stability in human bone cells. Arch Biochem Biophys. 1991;291(2):316–25.PubMedCrossRefGoogle Scholar
  134. 134.
    Irving JT, Wuthier RE. Histochemistry and biochemistry of calcification with special reference to the role of lipids. Clin Orthop. 1968;56:237–60.PubMedCrossRefGoogle Scholar
  135. 135.
    Howell DS, Marquez JF, Pita JC. The nature of phospholipids in normal and rachitic costochondral plates. Arthritis Rheum. 1965;8(6):1039–46.PubMedCrossRefGoogle Scholar
  136. 136.
    Dean DD, Boyan BD, Muniz OE, Howell DS, Schwartz Z. Vitamin D metabolites regulate matrix vesicle metalloproteinase content in a cell maturation-dependent manner. Calcif Tissue Int. 1996;59(2):109–16.PubMedCrossRefGoogle Scholar
  137. 137.
    Roughley PJ, Dickson IR. A comparison of proteoglycan from chick cartilage of different types and a study of the effect of vitamin D on proteoglycan structure. Connect Tissue Res. 1986;14(3):187–97.PubMedCrossRefGoogle Scholar
  138. 138.
    Boyan BD, Schwartz Z, Carnes DL Jr, Ramirez V. The effects of vitamin D metabolites on the plasma and matrix vesicle membranes of growth and resting cartilage cells in vitro. Endocrinology. 1988;122(6):2851–60.PubMedCrossRefGoogle Scholar
  139. 139.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Naja RP, Dardenne O, Arabian A, St Arnaud R. Chondrocyte-specific modulation of Cyp27b1 expression supports a role for local synthesis of 1,25-dihydroxyvitamin D3 in growth plate development. Endocrinology. 2009;150(9):4024–32.PubMedCrossRefGoogle Scholar
  141. 141.
    Owen TA, Aronow MS, Barone LM, Bettencourt B, Stein GS, Lian JB. Pleiotropic effects of vitamin D on osteoblast gene expression are related to the proliferative and differentiated state of the bone cell phenotype: dependency upon basal levels of gene expression, duration of exposure, and bone matrix competency in normal rat osteoblast cultures. Endocrinology. 1991;128(3):1496–504.PubMedCrossRefGoogle Scholar
  142. 142.
    Lian J, Stewart C, Puchacz E, Mackowiak S, Shalhoub V, Collart D, et al. Structure of the rat osteocalcin gene and regulation of vitamin D-dependent expression. Proc Natl Acad Sci U S A. 1989;86(4):1143–7.PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Demay MB, Gerardi JM, DeLuca HF, Kronenberg HM. DNA sequences in the rat osteocalcin gene that bind the 1,25-dihydroxyvitamin D3 receptor and confer responsiveness to 1,25-dihydroxyvitamin D3. Proc Natl Acad Sci U S A. 1990;87(1):369–73.PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Kerner SA, Scott RA, Pike JW. Sequence elements in the human osteocalcin gene confer basal activation and inducible response to hormonal vitamin D3. Proc Natl Acad Sci U S A. 1989;86(12):4455–9.PubMedPubMedCentralCrossRefGoogle Scholar
  145. 145.
    Noda M, Vogel RL, Craig AM, Prahl J, DeLuca HF, Denhardt DT. Identification of a DNA sequence responsible for binding of the 1,25-dihydroxyvitamin D3 receptor and 1,25-dihydroxyvitamin D3 enhancement of mouse secreted phosphoprotein 1 (SPP-1 or osteopontin) gene expression. Proc Natl Acad Sci U S A. 1990;87(24):9995–9.PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    Zhang R, Ducy P, Karsenty G. 1,25-dihydroxyvitamin D3 inhibits Osteocalcin expression in mouse through an indirect mechanism. J Biol Chem. 1997;272(1):110–6.PubMedCrossRefGoogle Scholar
  147. 147.
    Wronski TJ, Halloran BP, Bikle DD, Globus RK, Morey-Holton ER. Chronic administration of 1,25-dihydroxyvitamin D3: increased bone but impaired mineralization. Endocrinology. 1986;119(6):2580–5.PubMedCrossRefGoogle Scholar
  148. 148.
    Hock JM, Gunness-Hey M, Poser J, Olson H, Bell NH, Raisz LG. Stimulation of undermineralized matrix formation by 1,25 dihydroxyvitamin D3 in long bones of rats. Calcif Tissue Int. 1986;38(2):79–86.PubMedCrossRefGoogle Scholar
  149. 149.
    Suda T, Masuyama R, Bouillon R, Carmeliet G. Physiological functions of vitamin D: what we have learned from global and conditional VDR knockout mouse studies. Curr Opin Pharmacol. 2015;22:87–99.PubMedCrossRefGoogle Scholar
  150. 150.
    Yamamoto Y, Yoshizawa T, Fukuda T, Shirode-Fukuda Y, Yu T, Sekine K, et al. Vitamin D receptor in osteoblasts is a negative regulator of bone mass control. Endocrinology. 2013;154(3):1008–20.PubMedCrossRefGoogle Scholar
  151. 151.
    Suda T, Takahashi N, Abe E. Role of vitamin D in bone resorption. J Cell Biochem. 1992;49(1):53–8.PubMedCrossRefGoogle Scholar
  152. 152.
    Merke J, Klaus G, Hugel U, Waldherr R, Ritz E. No 1,25-dihydroxyvitamin D3 receptors on osteoclasts of calcium-deficient chicken despite demonstrable receptors on circulating monocytes. J Clin Invest. 1986;77(1):312–4.PubMedPubMedCentralCrossRefGoogle Scholar
  153. 153.
    Mee AP, Hoyland JA, Braidman IP, Freemont AJ, Davies M, Mawer EB. Demonstration of vitamin D receptor transcripts in actively resorbing osteoclasts in bone sections. Bone. 1996;18(4):295–9.PubMedCrossRefGoogle Scholar
  154. 154.
    Rodan GA, Martin TJ. Role of osteoblasts in hormonal control of bone resorption—a hypothesis. Calcif Tissue Int. 1981;33(4):349–51.PubMedCrossRefGoogle Scholar
  155. 155.
    Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev. 1999;20(3):345–57.PubMedCrossRefGoogle Scholar
  156. 156.
    Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A. 1998;95(7):3597–602.PubMedPubMedCentralCrossRefGoogle Scholar
  157. 157.
    Winaver J, Sylk DB, Robertson JS, Chen TC, Puschett JB. Micropuncture study of the acute renal tubular transport effects of 25-hydroxyvitamin D3 in the dog. Miner Electrolyte Metab. 1980;4:178–88.Google Scholar
  158. 158.
    Tenenhouse HS. Cellular and molecular mechanisms of renal phosphate transport. J Bone Miner Res. 1997;12(2):159–64.PubMedCrossRefGoogle Scholar
  159. 159.
    Erben RG, Andrukhova O. FGF23-Klotho signaling axis in the kidney. Bone. 2017;100:62–8.PubMedCrossRefGoogle Scholar
  160. 160.
    Puschett JB, Beck WS Jr, Jelonek A, Fernandez PC. Study of the renal tubular interactions of thyrocalcitonin, cyclic adenosine 3′,5′-monophosphate, 25-hydroxycholecalciferol, and calcium ion. J Clin Invest. 1974;53(3):756–67.PubMedPubMedCentralCrossRefGoogle Scholar
  161. 161.
    Puschett JB, Fernandez PC, Boyle IT, Gray RW, Omdahl JL, DeLuca HF. The acute renal tubular effects of 1,25-dihydroxycholecalciferol. Proc Soc Exp Biol Med. 1972;141(1):379–84.PubMedCrossRefGoogle Scholar
  162. 162.
    Puschett JB, Moranz J, Kurnick WS. Evidence for a direct action of cholecalciferol and 25-hydroxycholecalciferol on the renal transport of phosphate, sodium, and calcium. J Clin Invest. 1972;51(2):373–85.PubMedPubMedCentralCrossRefGoogle Scholar
  163. 163.
    Popovtzer MM, Robinette JB, DeLuca HF, Holick MF. The acute effect of 25-hydroxycholecalciferol on renal handling of phosphorus. Evidence for a parathyroid hormone-dependent mechanism. J Clin Invest. 1974;53(3):913–21.PubMedPubMedCentralCrossRefGoogle Scholar
  164. 164.
    Yamamoto M, Kawanobe Y, Takahashi H, Shimazawa E, Kimura S, Ogata E. Vitamin D deficiency and renal calcium transport in the rat. J Clin Invest. 1984;74(2):507–13.PubMedPubMedCentralCrossRefGoogle Scholar
  165. 165.
    Lambers TT, Bindels RJ, Hoenderop JG. Coordinated control of renal Ca2+ handling. Kidney Int. 2006;69(4):650–4.PubMedCrossRefGoogle Scholar
  166. 166.
    Kumar R, Schaefer J, Grande JP, Roche PC. Immunolocalization of calcitriol receptor, 24-hydroxylase cytochrome P-450, and calbindin D28k in human kidney. Am J Phys. 1994;266(3 Pt 2):F477–85.Google Scholar
  167. 167.
    Borke JL, Minami J, Verma AK, Penniston JT, Kumar R. Co-localization of erythrocyte Ca++-Mg++ ATPase and vitamin D-dependent 28-kDa-calcium binding protein. Kidney Int. 1988;34(2):262–7.PubMedCrossRefGoogle Scholar
  168. 168.
    Peterlik M, Wasserman RH. Regulation by vitamin D of intestinal phosphate absorption. Horm Metab Res. 1980;12(5):216–9.PubMedCrossRefGoogle Scholar
  169. 169.
    Christakos S, Brunette MG, Norman AW. Localization of immunoreactive vitamin D-dependent calcium binding protein in chick nephron. Endocrinology. 1981;109(1):322–4.PubMedCrossRefGoogle Scholar
  170. 170.
    Roth J, Thorens B, Hunziker W, Norman AW, Orci L. Vitamin D--dependent calcium binding protein: immunocytochemical localization in chick kidney. Science. 1981;214(4517):197–200.PubMedCrossRefGoogle Scholar
  171. 171.
    Song Y, Peng X, Porta A, Takanaga H, Peng JB, Hediger MA, et al. Calcium transporter 1 and epithelial calcium channel messenger ribonucleic acid are differentially regulated by 1,25 dihydroxyvitamin D3 in the intestine and kidney of mice. Endocrinology. 2003;144(9):3885–94.PubMedCrossRefGoogle Scholar
  172. 172.
    Biber J, Hernando N, Forster I. Phosphate transporters and their function. Annu Rev Physiol. 2013;75:535–50.PubMedCrossRefGoogle Scholar
  173. 173.
    Lehmann B, Tiebel O, Meurer M. Expression of vitamin D3 25-hydroxylase (CYP27) mRNA after induction by vitamin D3 or UVB radiation in keratinocytes of human skin equivalents—a preliminary study. Arch Dermatol Res. 1999;291(9):507–10.PubMedCrossRefGoogle Scholar
  174. 174.
    Vantieghem K, De Haes P, Bouillon R, Segaert S. Dermal fibroblasts pretreated with a sterol Delta7-reductase inhibitor produce 25-hydroxyvitamin D3 upon UVB irradiation. J Photochem Photobiol B. 2006;85(1):72–8.PubMedCrossRefGoogle Scholar
  175. 175.
    Bikle DD, Nemanic MK, Gee E, Elias P. 1,25-Dihydroxyvitamin D3 production by human keratinocytes. Kinetics and regulation. J Clin Invest. 1986;78(2):557–66.PubMedPubMedCentralCrossRefGoogle Scholar
  176. 176.
    Bikle DD, Halloran BP, Riviere JE. Production of 1,25 dihydroxyvitamin D3 by perfused pig skin. J Invest Dermatol. 1994;102(5):796–8.PubMedCrossRefGoogle Scholar
  177. 177.
    Xie Z, Munson S, Huang N, Schuster I, Portale AA, Miller WL, et al. The mechanism of 1,25-dihydroxyvitamin D3 auto-regulation in keratinocytes. J Bone Min Res (Program & Abstracts). 2001;16(Suppl 1):S556.Google Scholar
  178. 178.
    Zehnder D, Bland R, Williams MC, McNinch RW, Howie AJ, Stewart PM, et al. Extrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylase. J Clin Endocrinol Metab. 2001;86(2):888–94.PubMedGoogle Scholar
  179. 179.
    Pillai S, Bikle DD, Elias PM. 1,25-Dihydroxyvitamin D production and receptor binding in human keratinocytes varies with differentiation. J Biol Chem. 1988;263(11):5390–5.PubMedGoogle Scholar
  180. 180.
    Bikle DD. Vitamin D and the skin: physiology and pathophysiology. Rev Endocr Metab Disord. 2012;13(1):3–19.PubMedPubMedCentralCrossRefGoogle Scholar
  181. 181.
    Ratnam AV, Cho JK, Bikle DD. 1,25-dihydroxyvitamin D3 enhances the calcium response of keratinocytes. J Invest Dermatol. 1996;106:910.CrossRefGoogle Scholar
  182. 182.
    Yuspa SH, Kilkenny AE, Steinert PM, Roop DR. Expression of murine epidermal differentiation markers is tightly regulated by restricted extracellular calcium concentrations in vitro. J Cell Biol. 1989;109(3):1207–17.PubMedCrossRefGoogle Scholar
  183. 183.
    Rice RH, Green H. Presence in human epidermal cells of a soluble protein precursor of the cross-linked envelope: activation of the cross-linking by calcium ions. Cell. 1979;18(3):681–94.PubMedCrossRefGoogle Scholar
  184. 184.
    Hohl D, Lichti U, Breitkreutz D, Steinert PM, Roop DR. Transcription of the human loricrin gene in vitro is induced by calcium and cell density and suppressed by retinoic acid. J Invest Dermatol. 1991;96(4):414–8.PubMedCrossRefGoogle Scholar
  185. 185.
    Simon M, Green H. Participation of membrane-associated proteins in the formation of the cross-linked envelope of the keratinocyte. Cell. 1984;36(4):827–34.PubMedCrossRefGoogle Scholar
  186. 186.
    Hohl D. Cornified cell envelope. Dermatologica. 1990;180(4):201–11.PubMedCrossRefGoogle Scholar
  187. 187.
    Thacher SM, Rice RH. Keratinocyte-specific transglutaminase of cultured human epidermal cells: relation to cross-linked envelope formation and terminal differentiation. Cell. 1985;40(3):685–95.PubMedCrossRefGoogle Scholar
  188. 188.
    Hennings H, Steinert P, Buxman MM. Calcium induction of transglutaminase and the formation of epsilon(gamma-glutamyl) lysine cross-links in cultured mouse epidermal cells. Biochem Biophys Res Commun. 1981;102(2):739–45.PubMedCrossRefGoogle Scholar
  189. 189.
    Su MJ, Bikle DD, Mancianti ML, Pillai S. 1,25-Dihydroxyvitamin D3 potentiates the keratinocyte response to calcium. J Biol Chem. 1994;269(20):14723–9.PubMedGoogle Scholar
  190. 190.
    Smith EL, Walworth NC, Holick MF. Effect of 1 alpha,25-dihydroxyvitamin D3 on the morphologic and biochemical differentiation of cultured human epidermal keratinocytes grown in serum-free conditions. J Invest Dermatol. 1986;86(6):709–14.PubMedCrossRefGoogle Scholar
  191. 191.
    Pillai S, Bikle DD. Role of intracellular-free calcium in the cornified envelope formation of keratinocytes: differences in the mode of action of extracellular calcium and 1,25 dihydroxyvitamin D3. J Cell Physiol. 1991;146(1):94–100.PubMedCrossRefGoogle Scholar
  192. 192.
    McLane JA, Katz M, Abdelkader N. Effect of 1,25-dihydroxyvitamin D3 on human keratinocytes grown under different culture conditions. In Vitro Cell Dev Biol. 1990;26(4):379–87.PubMedCrossRefGoogle Scholar
  193. 193.
    Oda Y, Uchida Y, Moradian S, Crumrine D, Elias PM, Bikle DD. Vitamin D receptor and coactivators SRC2 and 3 regulate epidermis-specific sphingolipid production and permeability barrier formation. J Invest Dermatol. 2009;129(6):1367–78.PubMedCrossRefGoogle Scholar
  194. 194.
    Tu CL, Crumrine DA, Man MQ, Chang W, Elalieh H, You M, et al. Ablation of the calcium-sensing receptor in keratinocytes impairs epidermal differentiation and barrier function. J Invest Dermatol. 2012;132(10):2350–9.PubMedPubMedCentralCrossRefGoogle Scholar
  195. 195.
    Schauber J, Dorschner RA, Coda AB, Buchau AS, Liu PT, Kiken D, et al. Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism. J Clin Invest. 2007;117(3):803–11.PubMedPubMedCentralCrossRefGoogle Scholar
  196. 196.
    Oda Y, Sihlbom C, Huang L, Rachez C, Chang CP, Burlingame AL, et al. Sequential utilization of the VDR coactivators, DRIP/Mediator and SRC/p160, during keratinocyte differentiation. Mol Endocrinol. 2003;17:2329–39.PubMedCrossRefGoogle Scholar
  197. 197.
    Tu CL, Chang W, Bikle DD. The extracellular calcium-sensing receptor is required for calcium-induced differentiation in human keratinocytes. J Biol Chem. 2001;276(44):41079–85.PubMedCrossRefGoogle Scholar
  198. 198.
    Tu CL, Chang W, Bikle DD. Phospholipase cgamma1 is required for activation of store-operated channels in human keratinocytes. J Invest Dermatol. 2005;124(1):187–97.PubMedCrossRefGoogle Scholar
  199. 199.
    Tu C, Chang W, Xie Z, Bikle DD. Inactivation of the calcium sensing receptor inhibits E-cadherin-mediated cell-cell adhesion and calcium-induced differentiation in human epidermal keratinocytes. J Biol Chem. 2008;283(6):3519–28.PubMedCrossRefGoogle Scholar
  200. 200.
    Xie Z, Singleton PA, Bourguignon LY, Bikle DD. Calcium-induced human keratinocyte differentiation requires src- and fyn-mediated phosphatidylinositol 3-kinase-dependent activation of phospholipase C-gamma1. Mol Biol Cell. 2005;16(7):3236–46.PubMedPubMedCentralCrossRefGoogle Scholar
  201. 201.
    Xie Z, Bikle DD. The recruitment of phosphatidylinositol 3-kinase to the E-cadherin-catenin complex at the plasma membrane is required for calcium-induced phospholipase C-gamma1 activation and human keratinocyte differentiation. J Biol Chem. 2007;282(12):8695–703.PubMedCrossRefGoogle Scholar
  202. 202.
    Xie Z, Chang SM, Pennypacker SD, Liao EY, Bikle DD. Phosphatidylinositol-4-phosphate 5-kinase 1alpha mediates extracellular calcium-induced keratinocyte differentiation. Mol Biol Cell. 2009;20(6):1695–704.PubMedPubMedCentralCrossRefGoogle Scholar
  203. 203.
    Pillai S, Bikle DD. Adenosine triphosphate stimulates phosphoinositide metabolism, mobilizes intracellular calcium, and inhibits terminal differentiation of human epidermal keratinocytes. J Clin Invest. 1992;90(1):42–51.PubMedPubMedCentralCrossRefGoogle Scholar
  204. 204.
    Yang LC, Ng DC, Bikle DD. Role of protein kinase C alpha in calcium induced keratinocyte differentiation: defective regulation in squamous cell carcinoma. J Cell Physiol. 2003;195(2):249–59.PubMedCrossRefGoogle Scholar
  205. 205.
    Xie Z, Bikle DD. Cloning of the human phospholipase C-gamma1 promoter and identification of a DR6-type vitamin D-responsive element. J Biol Chem. 1997;272(10):6573–7.PubMedCrossRefGoogle Scholar
  206. 206.
    Tu CL, Chang W, Bikle DD. The role of the calcium sensing receptor in regulating intracellular calcium handling in human epidermal keratinocytes. J Invest Dermatol. 2007;127(5):1074–83.PubMedCrossRefGoogle Scholar
  207. 207.
    Bikle DD. Extraskeletal actions of vitamin D. Ann N Y Acad Sci. 2016;1376(1):29–52.PubMedPubMedCentralCrossRefGoogle Scholar
  208. 208.
    Santagata S, Thakkar A, Ergonul A, Wang B, Woo T, Hu R, et al. Taxonomy of breast cancer based on normal cell phenotype predicts outcome. J Clin Invest. 2014;124(2):859–70.PubMedPubMedCentralCrossRefGoogle Scholar
  209. 209.
    Matusiak D, Benya RV. CYP27A1 and CYP24 expression as a function of malignant transformation in the colon. J Histochem Cytochem. 2007;55(12):1257–64.PubMedCrossRefGoogle Scholar
  210. 210.
    Brozek W, Manhardt T, Kallay E, Peterlik M, Cross HS. Relative expression of vitamin D hydroxylases, CYP27B1 and CYP24A1, and of cyclooxygenase-2 and heterogeneity of human colorectal cancer in relation to age, gender, tumor location, and malignancy: results from factor and cluster analysis. Cancers. 2012;4(3):763–76.PubMedPubMedCentralCrossRefGoogle Scholar
  211. 211.
    Tannour-Louet M, Lewis SK, Louet JF, Stewart J, Addai JB, Sahin A, et al. Increased expression of CYP24A1 correlates with advanced stages of prostate cancer and can cause resistance to vitamin D3-based therapies. FASEB J. 2014;28(1):364–72.PubMedCrossRefGoogle Scholar
  212. 212.
    Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G. Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev. 2016;96(1):365–408.PubMedCrossRefGoogle Scholar
  213. 213.
    Chang S, Gao L, Yang Y, Tong D, Guo B, Liu L, et al. miR-145 mediates the antiproliferative and gene regulatory effects of vitamin D3 by directly targeting E2F3 in gastric cancer cells. Oncotarget. 2015;6(10):7675–85.PubMedPubMedCentralGoogle Scholar
  214. 214.
    Gocek E, Wang X, Liu X, Liu CG, Studzinski GP. MicroRNA-32 upregulation by 1,25-dihydroxyvitamin D3 in human myeloid leukemia cells leads to Bim targeting and inhibition of AraC-induced apoptosis. Cancer Res. 2011;71(19):6230–9.PubMedPubMedCentralCrossRefGoogle Scholar
  215. 215.
    Hager G, Formanek M, Gedlicka C, Thurnher D, Knerer B, Kornfehl J. 1,25(OH)2 vitamin D3 induces elevated expression of the cell cycle-regulating genes P21 and P27 in squamous carcinoma cell lines of the head and neck. Acta Otolaryngol. 2001;121(1):103–9.PubMedCrossRefGoogle Scholar
  216. 216.
    Palmer HG, Sanchez-Carbayo M, Ordonez-Moran P, Larriba MJ, Cordon-Cardo C, Munoz A. Genetic signatures of differentiation induced by 1alpha,25-dihydroxyvitamin D3 in human colon cancer cells. Cancer Res. 2003;63(22):7799–806.PubMedGoogle Scholar
  217. 217.
    An BS, Tavera-Mendoza LE, Dimitrov V, Wang X, Calderon MR, Wang HJ, et al. Stimulation of Sirt1-regulated FoxO protein function by the ligand-bound vitamin D receptor. Mol Cell Biol. 2010;30(20):4890–900.PubMedPubMedCentralCrossRefGoogle Scholar
  218. 218.
    Colston KW, Perks CM, Xie SP, Holly JM. Growth inhibition of both MCF-7 and Hs578T human breast cancer cell lines by vitamin D analogues is associated with increased expression of insulin-like growth factor binding protein-3. J Mol Endocrinol. 1998;20(1):157–62.PubMedCrossRefGoogle Scholar
  219. 219.
    Huynh H, Pollak M, Zhang JC. Regulation of insulin-like growth factor (IGF) II and IGF binding protein 3 autocrine loop in human PC-3 prostate cancer cells by vitamin D metabolite 1,25(OH)2D3 and its analog EB1089. Int J Oncol. 1998;13(1):137–43.PubMedGoogle Scholar
  220. 220.
    Peehl DM, Shinghal R, Nonn L, Seto E, Krishnan AV, Brooks JD, et al. Molecular activity of 1,25-dihydroxyvitamin D3 in primary cultures of human prostatic epithelial cells revealed by cDNA microarray analysis. J Steroid Biochem Mol Biol. 2004;92(3):131–41.PubMedCrossRefGoogle Scholar
  221. 221.
    Swami S, Raghavachari N, Muller UR, Bao YP, Feldman D. Vitamin D growth inhibition of breast cancer cells: gene expression patterns assessed by cDNA microarray. Breast Cancer Res Treat. 2003;80(1):49–62.PubMedCrossRefGoogle Scholar
  222. 222.
    Yang L, Yang J, Venkateswarlu S, Ko T, Brattain MG. Autocrine TGFbeta signaling mediates vitamin D3 analog-induced growth inhibition in breast cells. J Cell Physiol. 2001;188(3):383–93.PubMedCrossRefGoogle Scholar
  223. 223.
    Aszterbaum M, Rothman A, Johnson RL, Fisher M, Xie J, Bonifas JM, et al. Identification of mutations in the human PATCHED gene in sporadic basal cell carcinomas and in patients with the basal cell nevus syndrome. J Invest Dermatol. 1998;110(6):885–8.PubMedCrossRefGoogle Scholar
  224. 224.
    Teichert AE, Elalieh H, Elias PM, Welsh J, Bikle DD. Overexpression of hedgehog signaling is associated with epidermal tumor formation in vitamin D receptor-null mice. J Invest Dermatol. 2011;131(11):2289–97.PubMedPubMedCentralCrossRefGoogle Scholar
  225. 225.
    McGaffin KR, Chrysogelos SA. Identification and characterization of a response element in the EGFR promoter that mediates transcriptional repression by 1,25-dihydroxyvitamin D3 in breast cancer cells. J Mol Endocrinol. 2005;35(1):117–33.PubMedCrossRefGoogle Scholar
  226. 226.
    Byers SW, Rowlands T, Beildeck M, Bong YS. Mechanism of action of vitamin D and the vitamin D receptor in colorectal cancer prevention and treatment. Rev Endocr Metab Disord. 2011;13(1):31–8.CrossRefGoogle Scholar
  227. 227.
    Aguilera O, Pena C, Garcia JM, Larriba MJ, Ordonez-Moran P, Navarro D, et al. The Wnt antagonist DICKKOPF-1 gene is induced by 1alpha,25-dihydroxyvitamin D3 associated to the differentiation of human colon cancer cells. Carcinogenesis. 2007;28(9):1877–84.PubMedCrossRefGoogle Scholar
  228. 228.
    Pendas-Franco N, Garcia JM, Pena C, Valle N, Palmer HG, Heinaniemi M, et al. DICKKOPF-4 is induced by TCF/beta-catenin and upregulated in human colon cancer, promotes tumour cell invasion and angiogenesis and is repressed by 1alpha,25-dihydroxyvitamin D3. Oncogene. 2008;27(32):4467–77.PubMedCrossRefGoogle Scholar
  229. 229.
    Diaz GD, Paraskeva C, Thomas MG, Binderup L, Hague A. Apoptosis is induced by the active metabolite of vitamin D3 and its analogue EB1089 in colorectal adenoma and carcinoma cells: possible implications for prevention and therapy. Cancer Res. 2000;60(8):2304–12.PubMedPubMedCentralGoogle Scholar
  230. 230.
    Pan L, Matloob AF, Du J, Pan H, Dong Z, Zhao J, et al. Vitamin D stimulates apoptosis in gastric cancer cells in synergy with trichostatin A/sodium butyrate-induced and 5-aza-2′-deoxycytidine-induced PTEN upregulation. FEBS J. 2010;277(4):989–99.PubMedCrossRefGoogle Scholar
  231. 231.
    Kizildag S, Ates H, Kizildag S. Treatment of K562 cells with 1,25-dihydroxyvitamin D3 induces distinct alterations in the expression of apoptosis-related genes BCL2, BAX, BCLXL, and p21. Ann Hematol. 2009;89(1):1–7.PubMedCrossRefGoogle Scholar
  232. 232.
    Weitsman GE, Ravid A, Liberman UA, Koren R. Vitamin D enhances caspase-dependent and independent TNF-induced breast cancer cell death: the role of reactive oxygen species. Ann N Y Acad Sci. 2003;1010:437–40.PubMedCrossRefGoogle Scholar
  233. 233.
    Weitsman GE, Koren R, Zuck E, Rotem C, Liberman UA, Ravid A. Vitamin D sensitizes breast cancer cells to the action of H2O2: mitochondria as a convergence point in the death pathway. Free Radic Biol Med. 2005;39(2):266–78.PubMedCrossRefGoogle Scholar
  234. 234.
    Newmark HL, Yang K, Kurihara N, Fan K, Augenlicht LH, Lipkin M. Western-style diet-induced colonic tumors and their modulation by calcium and vitamin D in C57Bl/6 mice: a preclinical model for human sporadic colon cancer. Carcinogenesis. 2009;30(1):88–92.PubMedPubMedCentralCrossRefGoogle Scholar
  235. 235.
    Murillo G, Nagpal V, Tiwari N, Benya RV, Mehta RG. Actions of vitamin D are mediated by the TLR4 pathway in inflammation-induced colon cancer. J Steroid Biochem Mol Biol. 2003;121(1–2):403–7.Google Scholar
  236. 236.
    Yang K, Lamprecht SA, Shinozaki H, Fan K, Yang W, Newmark HL, et al. Dietary calcium and cholecalciferol modulate cyclin D1 expression, apoptosis, and tumorigenesis in intestine of adenomatous polyposis coli1638N/+ mice. J Nutr. 2008;138(9):1658–63.PubMedCrossRefGoogle Scholar
  237. 237.
    Xu H, Posner GH, Stevenson M, Campbell FC. Apc(MIN) modulation of vitamin D secosteroid growth control. Carcinogenesis. 2010;31(8):1434–41.PubMedPubMedCentralCrossRefGoogle Scholar
  238. 238.
    Zheng W, Wong KE, Zhang Z, Dougherty U, Mustafi R, Kong J, et al. Inactivation of the vitamin D receptor in APC(min/+) mice reveals a critical role for the vitamin D receptor in intestinal tumor growth. Int J Cancer. 2011;130(1):10–9.PubMedPubMedCentralCrossRefGoogle Scholar
  239. 239.
    Lipkin M, Newmark HL. Vitamin D, calcium and prevention of breast cancer: a review. J Am Coll Nutr. 1999;18(5 Suppl):392S–7S.PubMedCrossRefGoogle Scholar
  240. 240.
    Zinser GM, Welsh J. Effect of Vitamin D3 receptor ablation on murine mammary gland development and tumorigenesis. J Steroid Biochem Mol Biol. 2004;89–90(1–5):433–6.PubMedCrossRefGoogle Scholar
  241. 241.
    VanWeelden K, Flanagan L, Binderup L, Tenniswood M, Welsh J. Apoptotic regression of MCF-7 xenografts in nude mice treated with the vitamin D3 analog, EB1089. Endocrinology. 1998;139(4):2102–10.PubMedCrossRefGoogle Scholar
  242. 242.
    Bhatia V, Saini MK, Shen X, Bi LX, Qiu S, Weigel NL, et al. EB1089 inhibits the parathyroid hormone-related protein-enhanced bone metastasis and xenograft growth of human prostate cancer cells. Mol Cancer Ther. 2009;8(7):1787–98.PubMedPubMedCentralCrossRefGoogle Scholar
  243. 243.
    Zheng Y, Zhou H, Ooi LL, Snir AD, Dunstan CR, Seibel MJ. Vitamin D deficiency promotes prostate cancer growth in bone. Prostate. 2011;71(9):1012–21.PubMedCrossRefGoogle Scholar
  244. 244.
    Mordan-McCombs S, Brown T, Wang WL, Gaupel AC, Welsh J, Tenniswood M. Tumor progression in the LPB-Tag transgenic model of prostate cancer is altered by vitamin D receptor and serum testosterone status. J Steroid Biochem Mol Biol. 2010;121(1–2):368–71.PubMedPubMedCentralCrossRefGoogle Scholar
  245. 245.
    Krishnan AV, Trump DL, Johnson CS, Feldman D. The role of vitamin D in cancer prevention and treatment. Endocrinol Metab Clin North Am. 2010;39(2):401–18, table of contents.PubMedPubMedCentralCrossRefGoogle Scholar
  246. 246.
    Ellison TI, Smith MK, Gilliam AC, Macdonald PN. Inactivation of the vitamin D receptor enhances susceptibility of murine skin to UV-induced tumorigenesis. J Invest Dermatol. 2008;128:2508–17.PubMedPubMedCentralCrossRefGoogle Scholar
  247. 247.
    Gupta R, Dixon KM, Deo SS, Holliday CJ, Slater M, Halliday GM, et al. Photoprotection by 1,25 dihydroxyvitamin D3 is associated with an increase in p53 and a decrease in nitric oxide products. J Invest Dermatol. 2007;127(3):707–15.PubMedCrossRefGoogle Scholar
  248. 248.
    Ma Y, Zhang P, Wang F, Yang J, Liu Z, Qin H. Association between vitamin D and risk of colorectal cancer: a systematic review of prospective studies. J Clin Oncol. 2011;29(28):3775–82.PubMedCrossRefGoogle Scholar
  249. 249.
    Yin L, Grandi N, Raum E, Haug U, Arndt V, Brenner H. Meta-analysis: serum vitamin D and colorectal adenoma risk. Prev Med. 2011;53(1–2):10–6.PubMedCrossRefGoogle Scholar
  250. 250.
    Shin MH, Holmes MD, Hankinson SE, Wu K, Colditz GA, Willett WC. Intake of dairy products, calcium, and vitamin d and risk of breast cancer. J Natl Cancer Inst. 2002;94(17):1301–11.PubMedCrossRefGoogle Scholar
  251. 251.
    Lin J, Manson JE, Lee IM, Cook NR, Buring JE, Zhang SM. Intakes of calcium and vitamin D and breast cancer risk in women. Arch Intern Med. 2007;167(10):1050–9.PubMedCrossRefGoogle Scholar
  252. 252.
    Chen P, Hu P, Xie D, Qin Y, Wang F, Wang H. Meta-analysis of vitamin D, calcium and the prevention of breast cancer. Breast Cancer Res Treat. 2010;121(2):469–77.PubMedCrossRefGoogle Scholar
  253. 253.
    Gandini S, Boniol M, Haukka J, Byrnes G, Cox B, Sneyd MJ, et al. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer. 2011;128(6):1414–24.PubMedCrossRefGoogle Scholar
  254. 254.
    van der Rhee HJ, de Vries E, Coebergh JW. Does sunlight prevent cancer? A systematic review. Eur J Cancer. 2006;42(14):2222–32.PubMedCrossRefGoogle Scholar
  255. 255.
    Gilbert R, Martin RM, Beynon R, Harris R, Savovic J, Zuccolo L, et al. Associations of circulating and dietary vitamin D with prostate cancer risk: a systematic review and dose-response meta-analysis. Cancer Causes Control. 2011;22(3):319–40.PubMedCrossRefGoogle Scholar
  256. 256.
    Tang JY, Parimi N, Wu A, Boscardin WJ, Shikany JM, Chren MM, et al. Inverse association between serum 25(OH) vitamin D levels and non-melanoma skin cancer in elderly men. Cancer Causes Control. 2010;21(3):387–91.PubMedCrossRefGoogle Scholar
  257. 257.
    Asgari MM, Tang J, Warton ME, Chren MM, Quesenberry CP Jr, Bikle D, et al. Association of prediagnostic serum vitamin D levels with the development of basal cell carcinoma. J Invest Dermatol. 2010;130(5):1438–43.PubMedCrossRefGoogle Scholar
  258. 258.
    Eide MJ, Johnson DA, Jacobsen GR, Krajenta RJ, Rao DS, Lim HW, et al. Vitamin D and nonmelanoma skin cancer in a health maintenance organization cohort. Arch Dermatol. 2011;147(12):1379–84.PubMedCrossRefGoogle Scholar
  259. 259.
    Demay MB, Kiernan MS, DeLuca HF, Kronenberg HM. Sequences in the human parathyroid hormone gene that bind the 1,25-dihydroxyvitamin D3 receptor and mediate transcriptional repression in response to 1,25-dihydroxyvitamin D3. Proc Natl Acad Sci U S A. 1992;89(17):8097–101.PubMedPubMedCentralCrossRefGoogle Scholar
  260. 260.
    Kim MS, Fujiki R, Murayama A, Kitagawa H, Yamaoka K, Yamamoto Y, et al. 1Alpha,25(OH)2D3-induced transrepression by vitamin D receptor through E-box-type elements in the human parathyroid hormone gene promoter. Mol Endocrinol (Baltimore, Md). 2007;21(2):334–42.CrossRefGoogle Scholar
  261. 261.
    Kim MS, Kondo T, Takada I, Youn MY, Yamamoto Y, Takahashi S, et al. DNA demethylation in hormone-induced transcriptional derepression. Nature. 2009;461(7266):1007–12.PubMedCrossRefGoogle Scholar
  262. 262.
    Sai AJ, Walters RW, Fang X, Gallagher JC. Relationship between vitamin D, parathyroid hormone, and bone health. J Clin Endocrinol Metab. 2011;96(3):E436–46.PubMedCrossRefGoogle Scholar
  263. 263.
    Ritter CS, Armbrecht HJ, Slatopolsky E, Brown AJ. 25-Hydroxyvitamin D(3) suppresses PTH synthesis and secretion by bovine parathyroid cells. Kidney Int. 2006;70(4):654–9.PubMedCrossRefGoogle Scholar
  264. 264.
    Meir T, Levi R, Lieben L, Libutti S, Carmeliet G, Bouillon R, et al. Deletion of the vitamin D receptor specifically in the parathyroid demonstrates a limited role for the receptor in parathyroid physiology. Am J Physiol Renal Physiol. 2009;297(5):F1192–8.PubMedCrossRefGoogle Scholar
  265. 265.
    Cheng Z, Tu C, Li A, Santa-Maria C, Ho H, You M, et al. Endocrine actions of parathyroid Cyp27b1 in the Ca2+ and skeletal homeostasis: studies of parathyroid-specific knockout mice. ASBMR Abstract. 2012;1108:S36.Google Scholar
  266. 266.
    Szabo A, Merke J, Beier E, Mall G, Ritz E. 1,25(OH)2 vitamin D3 inhibits parathyroid cell proliferation in experimental uremia. Kidney Int. 1989;35(4):1049–56.PubMedCrossRefGoogle Scholar
  267. 267.
    Liu W, Ridefelt P, Akerstrom G, Hellman P. Differentiation of human parathyroid cells in culture. J Endocrinol. 2001;168(3):417–25.PubMedCrossRefGoogle Scholar
  268. 268.
    Dusso A, Cozzolino M, Lu Y, Sato T, Slatopolsky E. 1,25-Dihydroxyvitamin D downregulation of TGFalpha/EGFR expression and growth signaling: a mechanism for the antiproliferative actions of the sterol in parathyroid hyperplasia of renal failure. J Steroid Biochem Mol Biol. 2004;89–90(1–5):507–11.PubMedCrossRefGoogle Scholar
  269. 269.
    Gogusev J, Duchambon P, Stoermann-Chopard C, Giovannini M, Sarfati E, Drueke TB. De novo expression of transforming growth factor-alpha in parathyroid gland tissue of patients with primary or secondary uraemic hyperparathyroidism. Nephrol Dial Transplant. 1996;11(11):2155–62.PubMedCrossRefGoogle Scholar
  270. 270.
    Cozzolino M, Lu Y, Finch J, Slatopolsky E, Dusso AS. p21WAF1 and TGF-alpha mediate parathyroid growth arrest by vitamin D and high calcium. Kidney Int. 2001;60(6):2109–17.PubMedCrossRefGoogle Scholar
  271. 271.
    Canaff L, Hendy GN. Human calcium-sensing receptor gene. Vitamin D response elements in promoters P1 and P2 confer transcriptional responsiveness to 1,25-dihydroxyvitamin D. J Biol Chem. 2002;277(33):30337–50.PubMedCrossRefGoogle Scholar
  272. 272.
    Canadillas S, Canalejo R, Rodriguez-Ortiz ME, Martinez-Moreno JM, Estepa JC, Zafra R, et al. Upregulation of parathyroid VDR expression by extracellular calcium is mediated by ERK1/2-MAPK signaling pathway. Am J Physiol Renal Physiol. 2010;298(5):F1197–204.PubMedCrossRefGoogle Scholar
  273. 273.
    Kadowaki S, Norman AW. Demonstration that the vitamin D metabolite 1,25(OH)2-vitamin D3 and not 24R,25(OH)2-vitamin D3 is essential for normal insulin secretion in the perfused rat pancreas. Diabetes. 1985;34(4):315–20.PubMedCrossRefGoogle Scholar
  274. 274.
    Lee S, Clark SA, Gill RK, Christakos S. 1,25-Dihydroxyvitamin D3 and pancreatic beta-cell function: vitamin D receptors, gene expression, and insulin secretion. Endocrinology. 1994;134(4):1602–10.PubMedCrossRefGoogle Scholar
  275. 275.
    Norman AW, Frankel JB, Heldt AM, Grodsky GM. Vitamin D deficiency inhibits pancreatic secretion of insulin. Science. 1980;209(4458):823–5.PubMedCrossRefGoogle Scholar
  276. 276.
    Zeitz U, Weber K, Soegiarto DW, Wolf E, Balling R, Erben RG. Impaired insulin secretory capacity in mice lacking a functional vitamin D receptor. FASEB J. 2003;17(3):509–11.PubMedCrossRefGoogle Scholar
  277. 277.
    Hagstrom E, Hellman P, Lundgren E, Lind L, Arnlov J. Serum calcium is independently associated with insulin sensitivity measured with euglycaemic-hyperinsulinaemic clamp in a community-based cohort. Diabetologia. 2007;50(2):317–24.PubMedCrossRefGoogle Scholar
  278. 278.
    Gysemans C, van Etten E, Overbergh L, Giulietti A, Eelen G, Waer M, et al. Unaltered diabetes presentation in NOD mice lacking the vitamin D receptor. Diabetes. 2008;57(1):269–75.PubMedCrossRefGoogle Scholar
  279. 279.
    Clark SA, Stumpf WE, Sar M, DeLuca HF, Tanaka Y. Target cells for 1,25 dihydroxyvitamin D3 in the pancreas. Cell Tissue Res. 1980;209(3):515–20.PubMedCrossRefGoogle Scholar
  280. 280.
    Morrissey RL, Bucci TJ, Richard B, Empson N, Lufkin EG. Calcium-binding protein: its cellular localization in jejunum, kidney and pancreas. Proc Soc Exp Biol Med. 1975;149(1):56–60.PubMedCrossRefGoogle Scholar
  281. 281.
    Bland R, Markovic D, Hills CE, Hughes SV, Chan SL, Squires PE, et al. Expression of 25-hydroxyvitamin D3-1alpha-hydroxylase in pancreatic islets. J Steroid Biochem Mol Biol. 2004;89–90(1–5):121–5.PubMedCrossRefGoogle Scholar
  282. 282.
    Sooy K, Schermerhorn T, Noda M, Surana M, Rhoten WB, Meyer M, et al. Calbindin-D(28k) controls [Ca(2+)](i) and insulin release. Evidence obtained from calbindin-d(28k) knockout mice and beta cell lines. J Biol Chem. 1999;274(48):34343–9.PubMedCrossRefGoogle Scholar
  283. 283.
    Rabinovitch A, Suarez-Pinzon WL, Sooy K, Strynadka K, Christakos S. Expression of calbindin-D(28k) in a pancreatic islet beta-cell line protects against cytokine-induced apoptosis and necrosis. Endocrinology. 2001;142(8):3649–55.PubMedCrossRefGoogle Scholar
  284. 284.
    Cheng Q, Li YC, Boucher BJ, Leung PS. A novel role for vitamin D: modulation of expression and function of the local renin-angiotensin system in mouse pancreatic islets. Diabetologia. 2011;54(8):2077–81.PubMedCrossRefGoogle Scholar
  285. 285.
    Kolek OI, Hines ER, Jones MD, LeSueur LK, Lipko MA, Kiela PR, et al. 1alpha,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.PubMedCrossRefGoogle Scholar
  286. 286.
    Fukumoto S, Yamashita T. FGF23 is a hormone-regulating phosphate metabolism—unique biological characteristics of FGF23. Bone. 2007;40(5):1190–5.PubMedCrossRefGoogle Scholar
  287. 287.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  288. 288.
    Zhou C, Lu F, Cao K, Xu D, Goltzman D, Miao D. Calcium-independent and 1,25(OH)2D3-dependent regulation of the renin-angiotensin system in 1alpha-hydroxylase knockout mice. Kidney Int. 2008;74(2):170–9.CrossRefPubMedGoogle Scholar
  289. 289.
    Andrukhova O, Slavic S, Zeitz U, Riesen SC, Heppelmann MS, Ambrisko TD, et al. Vitamin D is a regulator of endothelial nitric oxide synthase and arterial stiffness in mice. Mol Endocrinol (Baltimore, Md). 2014;28(1):53–64.CrossRefGoogle Scholar
  290. 290.
    Xiang W, Kong J, Chen S, Cao LP, Qiao G, Zheng W, et al. Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems. Am J Physiol Endocrinol Metab. 2005;288(1):E125–32.PubMedCrossRefGoogle Scholar
  291. 291.
    Liu PT, Krutzik SR, Modlin RL. Therapeutic implications of the TLR and VDR partnership. Trends Mol Med. 2007;13(3):117–24.PubMedCrossRefGoogle Scholar
  292. 292.
    Bikle DD. Vitamin D and immune function: understanding common pathways. Curr Osteoporos Rep. 2009;7(2):58–63.PubMedCrossRefGoogle Scholar
  293. 293.
    Chen S, Sims GP, Chen XX, Gu YY, Chen S, Lipsky PE. Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol. 2007;179(3):1634–47.PubMedCrossRefGoogle Scholar
  294. 294.
    Sigmundsdottir H, Pan J, Debes GF, Alt C, Habtezion A, Soler D, et al. DCs metabolize sunlight-induced vitamin D3 to ‘program’ T cell attraction to the epidermal chemokine CCL27. Nat Immunol. 2007;8(3):285–93.PubMedCrossRefGoogle Scholar
  295. 295.
    van Etten E, Mathieu C. Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol. 2005;97(1–2):93–101.PubMedCrossRefGoogle Scholar
  296. 296.
    Daniel C, Sartory NA, Zahn N, Radeke HH, Stein JM. Immune modulatory treatment of trinitrobenzene sulfonic acid colitis with calcitriol is associated with a change of a T helper (Th) 1/Th17 to a Th2 and regulatory T cell profile. J Pharmacol Exp Ther. 2008;324(1):23–33.PubMedCrossRefGoogle Scholar
  297. 297.
    Joshi S, Pantalena LC, Liu XK, Gaffen SL, Liu H, Rohowsky-Kochan C, et al. 1,25-dihydroxyvitamin D(3) ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A. Mol Cell Biol. 2011;31(17):3653–69.PubMedPubMedCentralCrossRefGoogle Scholar
  298. 298.
    Palmer MT, Lee YK, Maynard CL, Oliver JR, Bikle DD, Jetten AM, et al. Lineage-specific effects of 1,25-dihydroxyvitamin D(3) on the development of effector CD4 T cells. J Biol Chem. 2011;286(2):997–1004.PubMedCrossRefGoogle Scholar
  299. 299.
    Keating P, Munim A, Hartmann JX. Effect of vitamin D on T-helper type 9 polarized human memory cells in chronic persistent asthma. Ann Allergy Asthma Immunol. 2014;112(2):154–62.PubMedCrossRefPubMedCentralGoogle Scholar
  300. 300.
    Gregori S, Casorati M, Amuchastegui S, Smiroldo S, Davalli AM, Adorini L. Regulatory T cells induced by 1 alpha,25-dihydroxyvitamin D3 and mycophenolate mofetil treatment mediate transplantation tolerance. J Immunol. 2001;167(4):1945–53.PubMedCrossRefGoogle Scholar
  301. 301.
    Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008;133(5):775–87.PubMedCrossRefGoogle Scholar
  302. 302.
    Alroy I, Towers TL, Freedman LP. Transcriptional repression of the interleukin-2 gene by vitamin D3: direct inhibition of NFATp/AP-1 complex formation by a nuclear hormone receptor. Mol Cell Biol. 1995;15(10):5789–99.PubMedPubMedCentralCrossRefGoogle Scholar
  303. 303.
    Cippitelli M, Santoni A. Vitamin D3: a transcriptional modulator of the interferon-gamma gene. Eur J Immunol. 1998;28(10):3017–30.PubMedCrossRefGoogle Scholar
  304. 304.
    Riis JL, Johansen C, Gesser B, Moller K, Larsen CG, Kragballe K, et al. 1alpha,25(OH)(2)D(3) regulates NF-kappaB DNA binding activity in cultured normal human keratinocytes through an increase in IkappaBalpha expression. Arch Dermatol Res. 2004;296(5):195–202.PubMedCrossRefGoogle Scholar
  305. 305.
    Adorini L, Penna G. Control of autoimmune diseases by the vitamin D endocrine system. Nat Clin Pract Rheumatol. 2008;4(8):404–12.PubMedCrossRefGoogle Scholar
  306. 306.
    Froicu M, Weaver V, Wynn TA, McDowell MA, Welsh JE, Cantorna MT. A crucial role for the vitamin D receptor in experimental inflammatory bowel diseases. Mol Endocrinol (Baltimore, Md). 2003;17(12):2386–92.CrossRefGoogle Scholar
  307. 307.
    Amuchastegui S, Daniel KC, Adorini L. Inhibition of acute and chronic allograft rejection in mouse models by BXL-628, a nonhypercalcemic vitamin D receptor agonist. Transplantation. 2005;80(1):81–7.PubMedCrossRefGoogle Scholar
  308. 308.
    Zhang Z, Hener P, Frossard N, Kato S, Metzger D, Li M, et al. Thymic stromal lymphopoietin overproduced by keratinocytes in mouse skin aggravates experimental asthma. Proc Natl Acad Sci U S A. 2009;106(5):1536–41.PubMedPubMedCentralCrossRefGoogle Scholar
  309. 309.
    Topilski I, Flaishon L, Naveh Y, Harmelin A, Levo Y, Shachar I. The anti-inflammatory effects of 1,25-dihydroxyvitamin D3 on Th2 cells in vivo are due in part to the control of integrin-mediated T lymphocyte homing. Eur J Immunol. 2004;34(4):1068–76.PubMedCrossRefGoogle Scholar
  310. 310.
    Wittke A, Weaver V, Mahon BD, August A, Cantorna MT. Vitamin D receptor-deficient mice fail to develop experimental allergic asthma. J Immunol. 2004;173(5):3432–6.PubMedCrossRefGoogle Scholar
  311. 311.
    Ehrchen J, Helming L, Varga G, Pasche B, Loser K, Gunzer M, et al. Vitamin D receptor signaling contributes to susceptibility to infection with Leishmania major. FASEB J. 2007;21(12):3208–18.PubMedCrossRefGoogle Scholar
  312. 312.
    Khader SA, Gaffen SL, Kolls JK. Th17 cells at the crossroads of innate and adaptive immunity against infectious diseases at the mucosa. Mucosal Immunol. 2009;2(5):403–11.PubMedPubMedCentralCrossRefGoogle Scholar
  313. 313.
    Rajapakse R, Mousli M, Pfaff AW, Uring-Lambert B, Marcellin L, Bronner C, et al. 1,25-Dihydroxyvitamin D3 induces splenocyte apoptosis and enhances BALB/c mice sensitivity to toxoplasmosis. J Steroid Biochem Mol Biol. 2005;96(2):179–85.PubMedCrossRefGoogle Scholar
  314. 314.
    Ryz NR, Patterson SJ, Zhang Y, Ma C, Huang T, Bhinder G, et al. Active vitamin D (1,25-dihydroxyvitamin D3) increases host susceptibility to Citrobacter rodentium by suppressing mucosal Th17 responses. Am J Physiol Gastrointest Liver Physiol. 2012;303(12):G1299–311.PubMedPubMedCentralCrossRefGoogle Scholar
  315. 315.
    Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311(5768):1770–3.PubMedCrossRefGoogle Scholar
  316. 316.
    Schauber J, Gallo RL. The vitamin D pathway: a new target for control of the skin’s immune response? Exp Dermatol. 2008;17(8):633–9.PubMedPubMedCentralCrossRefGoogle Scholar
  317. 317.
    Brightbill HD, Libraty DH, Krutzik SR, Yang RB, Belisle JT, Bleharski JR, et al. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science. 1999;285(5428):732–6.PubMedCrossRefGoogle Scholar
  318. 318.
    Martineau AR, Timms PM, Bothamley GH, Hanifa Y, Islam K, Claxton AP, et al. High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet. 2011;377(9761):242–50.PubMedPubMedCentralCrossRefGoogle Scholar
  319. 319.
    Salahuddin N, Ali F, Hasan Z, Rao N, Aqeel M, Mahmood F. Vitamin D accelerates clinical recovery from tuberculosis: results of the SUCCINCT Study [Supplementary Cholecalciferol in recovery from tuberculosis]. A randomized, placebo-controlled, clinical trial of vitamin D supplementation in patients with pulmonary tuberculosis’. BMC Infect Dis. 2013;13:22.PubMedPubMedCentralCrossRefGoogle Scholar
  320. 320.
    Daley P, Jagannathan V, John KR, Sarojini J, Latha A, Vieth R, et al. Adjunctive vitamin D for treatment of active tuberculosis in India: a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2015;15(5):528–34.PubMedCrossRefGoogle Scholar
  321. 321.
    Tukvadze N, Sanikidze E, Kipiani M, Hebbar G, Easley KA, Shenvi N, et al. High-dose vitamin D3 in adults with pulmonary tuberculosis: a double-blind randomized controlled trial. Am J Clin Nutr. 2015;102(5):1059–69.PubMedPubMedCentralCrossRefGoogle Scholar
  322. 322.
    Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, et al. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med. 2002;347(15):1151–60.PubMedCrossRefGoogle Scholar
  323. 323.
    Howell MD, Gallo RL, Boguniewicz M, Jones JF, Wong C, Streib JE, et al. Cytokine milieu of atopic dermatitis skin subverts the innate immune response to vaccinia virus. Immunity. 2006;24(3):341–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Medicine and DermatologyVA Medical Center and University of California San FranciscoSan FranciscoUSA

Personalised recommendations