Ann Lab Med.  2014 May;34(3):181-186. 10.3343/alm.2014.34.3.181.

Vitamin D Activities for Health Outcomes

Affiliations
  • 1School of Pharmacy and Medical Sciences, University of South Australia, Chemical Pathology Directorate and Hanson Institute, SA Pathology, Adelaide, Australia. Howard.Morris@health.sa.gov.au

Abstract

Reports describing significant health risks due to inadequate vitamin D status continue to generate considerable interest amongst the medical and lay communities alike. Recent research on the various molecular activities of the vitamin D system, including the nuclear vitamin D receptor and other receptors for 1,25-dihydroxyvitamin D and vitamin D metabolism, provides evidence that the vitamin D system carries out biological activities across a wide range of tissues similar to other nuclear receptor hormones. This knowledge provides physiological plausibility of the various health benefits claimed to be provided by vitamin D and supports the proposals for conducting clinical trials. The vitamin D system plays critical roles in the maintenance of plasma calcium and phosphate and bone mineral homeostasis. Recent evidence confirms that plasma calcium homeostasis is the critical factor modulating vitamin D activity. Vitamin D activities in the skeleton include stimulation or inhibition of bone resorption and inhibition or stimulation of bone formation. The three major bone cell types, which are osteoblasts, osteocytes and osteoclasts, can all respond to vitamin D via the classical nuclear vitamin D receptor and metabolize 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D to activate the vitamin D receptor and modulate gene expression. Dietary calcium intake interacts with vitamin D metabolism at both the renal and bone tissue levels to direct either a catabolic action on the bone through the endocrine system when calcium intake is inadequate or an anabolic action through a bone autocrine or paracrine system when calcium intake is sufficient.

Keyword

Vitamin D; Metabolic bone diseases; Osteomalacia; Osteoporosis; Bone fractures; Calcium; Dietary; 25-hydroxyvitamin D

MeSH Terms

Calcium/metabolism
Fractures, Bone/metabolism/pathology
Humans
Osteoporosis/metabolism/pathology
Protein Binding
Receptors, Calcitriol/genetics/metabolism
Vitamin D/analogs & derivatives/*metabolism
Calcium
Receptors, Calcitriol
Vitamin D

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Reference

1. National Health and Medical Research Council (NHMRC). NHMRC additional Levels of Evidence and Grades for Recommendations for Developers of guidelines. Available from: https://www.nhmrc.gov.au/_files_nhmrc/file/guidelines/developers/nhmrc_levels_grades_evidence_120423.pdf.
2. Holick MF. McCollum Award Lecture, 1994: vitamin D--new horizons for the 21st century. Am J Clin Nutr. 1994; 60:619–630. PMID: 8092101.
Article
3. Bischoff-Ferrari HA, Willett WC, Orav EJ, Lips P, Meunier PJ, Lyons RA, et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med. 2012; 367:40–49. PMID: 22762317.
Article
4. Ringe JD. The effect of vitamin D on falls and fractures. Scand J Clin Lab Invest Suppl. 2012; 243:73–78. PMID: 22536766.
5. Rush L, McCartney G, Walsh D, Mackay D. Vitamin D and subsequent all-age and premature mortality: a systematic review. BMC Public Health. 2013; 13:679. PMID: 23883271.
Article
6. Spedding S, Vanlint S, Morris H, Scragg R. Does vitamin D sufficiency equate to a single serum 25-hydroxyvitamin D level or are different levels required for non-skeletal diseases? Nutrients. 2013; 5:5127–5139. PMID: 24352091.
Article
7. Morris HA. Vitamin D 2013: Where do the hyperbole end and the facts begin? Nutr Diet. 2013; 70:5–6.
Article
8. Morris HA. Autocrine and paracrine actions of vitamin D. Clin Biochem Rev. 2010; 31:129–138. PMID: 21170259.
9. Ryan JW, Anderson PH, Turner AG, Morris HA. Vitamin D activities and metabolic bone disease. Clin Chim Acta. 2013; 425:148–152. PMID: 23911750.
Article
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. PMID: 20227497.
Article
11. Khanal RC. Membrane receptors for vitamin D metabolites. Crit Rev Eukaryot Gene Expr. 2007; 17:31–47. PMID: 17341182.
Article
12. Anderson PH, Turner AG, Morris HA. Vitamin D actions to regulate calcium and skeletal homeostasis. Clin Biochem. 2012; 45:880–886. PMID: 22414785.
Article
13. Anderson PH, Atkins GJ, Turner AG, Kogawa M, Findlay DM, Morris HA. Vitamin D metabolism within bone cells: effects on bone structure and strength. Mol Cell Endocrinol. 2011; 347:42–47. PMID: 21664230.
Article
14. Anderson PH, O'Loughlin PD, May BK, Morris HA. Modulation of CYP27B1 and CYP24 mRNA expression in bone is independent of circulating 1,25(OH)2D3 levels. Bone. 2005; 36:654–662. PMID: 15781002.
Article
15. Hendrix I, Anderson P, May B, Morris H. Regulation of gene expression by the CYP27B1 promoter-study of a transgenic mouse model. J Steroid Biochem Mol Biol. 2004; 89-90:139–142. PMID: 15225761.
Article
16. Bikle DD. Vitamin D and skin: Physiology and pathophysiology. Rev Endocr Metab Disord. 2012; 13:3–19. PMID: 21845365.
17. Atkins GJ, Anderson PH, Findlay DM, Welldon KJ, Vincent C, Zannettino AC, et al. Metabolism of vitamin D3 in human osteoblasts: evidence for autocrine and paracrine activities of 1 alpha,25-dihydroxyvitamin D3. Bone. 2007; 40:1517–1528. PMID: 17395559.
18. Yang D, Atkins GJ, Turner AG, Anderson PH, Morris HA. Differential effects of 1,25-dihydroxyvitamin D on mineralisation and differentiation in two different types of osteoblast-like cultures. J Steroid Biochem Mol Biol. 2013; 136:166–170. PMID: 23220547.
Article
19. Anderson PH, Sawyer RK, Moore AJ, May BK, O'Loughlin PD, Morris HA. Vitamin D depletion induces RANKL-mediated osteoclastogenesis and bone loss in a rodent model. J Bone Miner Res. 2008; 23:1789–1797. PMID: 18597628.
Article
20. Brozek W, Manhardt T, Kállay 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 (Basel). 2012; 4:763–776. PMID: 24213465.
Article
21. Krishnan AV, Swami S, Feldman D. Equivalent anticancer activities of dietary vitamin D and calcitriol in an animal model of breast cancer: importance of mammary CYP27B1 for treatment and prevention. J Steroid Biochem Mol Biol. 2013; 136:289–295. PMID: 22939886.
Article
22. Bookout AL, Jeong Y, Downes M, Yu RT, Evans RM, Mangelsdorf DJ. Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell. 2006; 126:789–799. PMID: 16923397.
23. 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. PMID: 18844852.
Article
24. Engel KB. The glucocorticoid receptor and the coregulator Brm selectively modulate each other's occupancy and activity in a gene-specific manner. Mol Cell Biol. 2011; 31:3267–3276. PMID: 21646426.
Article
25. Dwivedi PP, Hii CS, Ferrante A, Tan J, Der CJ, Omdahl JL, et al. Role of MAP kinases in the 1,25-dihydroxyvitamin D3-induced transactivation of the rat cytochrome P450C24 (CYP24) promoter. Specific functions for ERK1/ERK2 and ERK5. J Biol Chem. 2002; 277:29643–29653. PMID: 12048211.
26. Boland RL. VDR activation of intracellular signaling pathways in skeletal muscle. Mol Cell Endocrinol. 2011; 347:11–16. PMID: 21664245.
Article
27. 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 USA. 2004; 101:7392. PMID: 15123837.
Article
28. Bravo S, Paredes R, Izaurieta P, Lian JB, Stein JL, Stein GS, et al. The classic receptor for 1alpha,25-dihydroxy vitamin D3 is required for non-genomic actions of 1alpha,25-dihydroxy vitamin D3 in osteosarcoma cells. J Cell Biochem. 2006; 99:995–1000. PMID: 16927375.
29. Mulholland DJ, Dedhar S, Coetzee GA, Nelson CC. Interaction of nuclear receptors with the Wnt/beta-catenin/Tcf signaling axis: Wnt you like to know? Endocr Rev. 2005; 26:898–915. PMID: 16126938.
30. Rawadi G. Wnt signalling pathway: a new target for the treatment of osteoporosis. Expert Opin Ther Targets. 2005; 9:1063–1077. PMID: 16185158.
Article
31. Rosen JF, Fleischman AR, Finberg L, Hamstra A, DeLuca HF. Rickets with alopecia: an inborn error of vitamin D metabolism. J Pediatr. 1979; 94:729–735. PMID: 221630.
32. Liberman UA, Samuel R, Halabe A, Kauli R, Edelstein S, Weisman Y, et al. End-organ resistance to 1,25-dihydroxycholecalciferol. Lancet. 1980; 1:504–506. PMID: 6102232.
Article
33. Brooks MH, Bell NH, Love L, Stem PH, Orfei E, Queener SF, et al. Vitamin-D-dependent rickets type II. Resistance of target organs to 1,25-dihydroxyvitamin D. N Engl J Med. 1978; 298:996–999. PMID: 205789.
34. 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 USA. 1997; 94:9831–9835. PMID: 9275211.
Article
35. Amling M, Priemel M, Holzmann T, Chapin K, Rueger JM, Baron R, et al. Rescue of the skeletal phenotype of vitamin D receptor-ablated mice in the setting of normal mineral ion homeostasis: formal histmorphometric and biomechanical analyses. Endocrinology. 1999; 140:4982–4987. PMID: 10537122.
36. Lieben L, Masuyama R, Torrekens S, Van Looveren R, Schrooten J, Baatsen P, et al. Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization. J Clin Invest. 2012; 122:1803–1815. PMID: 22523068.
Article
37. Xue Y. Intestinal vitamin D receptor is required for normal calcium and bone metabolism in mice. Gastroenterology. 2009; 136:1317–1327. PMID: 19254681.
Article
38. Erben RG, Soegiarto DW, Weber K, Zeitz U, Lieberhertt M, Gniadecki R, et al. Deletion of deoxyribonucleic acid binding domain of the vitamin D receptor abrogates genomic and nongenomic functions of vitamin D. Mol Endocrinol. 2002; 16:1524–1537. PMID: 12089348.
Article
39. Cochran M, Coates PT, Morris HA. The effect of calcitriol on fasting urine calcium loss and renal tubular reabsorption of calcium in patients with mild renal failure--actions of a permissive hormone. Clin Nephrol. 2005; 64:98–102. PMID: 16114785.
40. 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; 279:16754–16766. PMID: 14739296.
41. 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; 154:1008–1020. PMID: 23389957.
Article
42. Lieben L, Masuyama R, Torrekens S, Van Looveren R, Schrooten J, Baasten P, et al. Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization. J Clin Invest. 2012; 122:1803–1815. PMID: 22523068.
Article
43. Gardiner EM, Baldock PA, Thomas GP, Sims NA, Henderson NK, Hollis B, et al. Increased formation and decreased resorption of bone in mice with elevated vitamin D receptor in mature cells of the osteoblastic lineage. FASEB J. 2000; 14:1908–1916. PMID: 11023975.
Article
44. Misof BM, Roschger P, Tesch W, Baldock PA, Valenta A, Messmer P, et al. Targeted overexpression of vitamin D receptor in osteoblasts increases calcium concentration without affecting structural properties of bone mineral crystals. Calcif Tissue Int. 2003; 73:251–257. PMID: 14667138.
Article
45. Anderson PH, Sawyer RK, Moore AJ, May BK, O'Loughlin PD, Morris HA. Vitamin D depletion induces RANKL-mediated osteoclastogenesis and bone loss in a rodent model. J Bone Miner Res. 2008; 23:1789–1797. PMID: 18597628.
Article
46. Lee AM, Sawyer RK, Moore AJ, Morris HA, O'Loughlin PD, Anderson PH. Adequate dietary vitamin D and calcium are both required to reduce bone turnover and increased bone mineral volume. J Steroid Biochem Mol Biol. 2013; 12. 02. pii: S0960-0760(13)00263-X. doi: 10.1016/j.jsbmb.2013.11.009. [Epub ahead of print].
Article
47. St-Arnaud R. Vitamin D metabolism, cartilage and bone fracture repair. Mol Cell Endocrinol. 2011; 347:48–54. PMID: 21664253.
Article
48. Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol. 2014; 2:76–89. PMID: 24622671.
Article
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