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Vitamin D and Its Role in Skeletal Muscle

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Abstract

This review discusses the clinical and laboratory studies that have examined a role of vitamin D in skeletal muscle. Many observational studies, mainly in older populations, indicate that vitamin D status is positively associated with muscle strength and physical performance and inversely associated with risk of falling. Clinical trials of vitamin D supplementation in older adults with low vitamin D status mostly report improvements in muscle performance and reductions in falls. The underlying mechanisms are probably both indirect via calcium and phosphate and direct via activation of the vitamin D receptor (VDR) on muscle cells by 1,25-dihydroxyvitamin D [1,25(OH)2D]. VDR activation at the genomic level regulates transcription of genes involved in calcium handling and muscle cell differentiation and proliferation. A putative membrane-associated VDR activates intracellular signaling pathways also involved in calcium handling and signaling and myogenesis. Additional evidence comes from VDR knockout mouse models with abnormal muscle morphology and physical function, and VDR polymorphisms which are associated with differences in muscle strength. Recent identification of CYP27B1 bioactivity in skeletal muscle cells and in regenerating adult mouse muscle lends support to the direct action of both 25-hydroxyvitamin D and 1,25(OH)2D in muscle. Despite these research advances, many questions remain. Further research is needed to fully characterize molecular mechanisms of vitamin D action on muscle cells downstream of the VDR, describe the effects on muscle morphology and contractility, and determine whether these molecular and cellular effects translate into clinical improvements in physical function.

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References

  1. DeLuca HF (2004) Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 80:1689S–1696S

    PubMed  CAS  Google Scholar 

  2. Reichel H, Koeffler HP, Norman AW (1989) The role of the vitamin D endocrine system in health and disease. New Engl J Med 320:980–991

    Article  PubMed  CAS  Google Scholar 

  3. Walters MR (1992) Newly identified actions of the vitamin D endocrine system. Endocr Rev 13:719–764

    PubMed  CAS  Google Scholar 

  4. Bikle DD (2010) Vitamin D: newly discovered actions require reconsideration of physiologic requirements. Trends Endocrinol Metab 21:375–384

    Article  PubMed  CAS  Google Scholar 

  5. Boland R (1986) Role of vitamin D in skeletal muscle function. Endocr Rev 7:434–448

    Article  PubMed  CAS  Google Scholar 

  6. Visser M, Deeg DJ, Lips P (2003) Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. J Clin Endocrinol Metab 88:5766–5772

    Article  PubMed  CAS  Google Scholar 

  7. Snijder MB, van Schoor NM, Pluijm SM, van Dam RM, Visser M, Lips P (2006) Vitamin D status in relation to one-year risk of recurrent falling in older men and women. J Clin Endocrinol Metab 91:2980–2985

    Article  PubMed  CAS  Google Scholar 

  8. Schubert L, DeLuca HF (2010) Hypophosphatemia is responsible for skeletal muscle weakness of vitamin D deficiency. Arch Biochem Biophys 500:157–161

    Article  PubMed  CAS  Google Scholar 

  9. Simpson RU, Thomas GA, Arnold AJ (1985) Identification of 1,25-dihydroxyvitamin D3 receptors and activities in muscle. J Biol Chem 260:8882–8891

    PubMed  CAS  Google Scholar 

  10. Bischoff HA, Borchers M, Gudat F, Duermueller U, Theiler R, Stahelin HB, Dick W (2001) In situ detection of 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle tissue. Histochem J 33:19–24

    Article  PubMed  CAS  Google Scholar 

  11. Dent CE, Richens A, Rowe DJ, Stamp TC (1970) Osteomalacia with long-term anticonvulsant therapy in epilepsy. Br Med J 4:69–72

    Article  PubMed  CAS  Google Scholar 

  12. Smith R, Stern G (1967) Myopathy, osteomalacia and hyperparathyroidism. Brain 90:593–602

    Article  PubMed  CAS  Google Scholar 

  13. Prineas JW, Mason AS, Henson RA (1965) Myopathy in metabolic bone disease. Br Med J 1:1034–1036

    Article  PubMed  CAS  Google Scholar 

  14. Marsden CD, Reynolds EH, Parsons V, Harris R, Duchen L (1973) Myopathy associated with anticonvulsant osteomalacia. Br Med J 4:526–527

    Article  PubMed  CAS  Google Scholar 

  15. Smith R, Stern G (1969) Muscular weakness in osteomalacia and hyperparathyroidism. J Neurol Sci 8:511–520

    Article  PubMed  CAS  Google Scholar 

  16. Wassner SJ, Li JB, Sperduto A, Norman ME (1983) Vitamin D deficiency, hypocalcemia, and increased skeletal muscle degradation in rats. J Clin Invest 72:102–112

    Article  PubMed  CAS  Google Scholar 

  17. Gloth FM 3rd, Tobin JD, Sherman SS, Hollis BW (1991) Is the recommended daily allowance for vitamin D too low for the homebound elderly? J Am Geriatr Soc 39:137–141

    PubMed  Google Scholar 

  18. Schott GD, Wills MR (1976) Muscle weakness in osteomalacia. Lancet 1(7960):626–629

    Article  PubMed  CAS  Google Scholar 

  19. Skaria J, Katiyar BC, Srivastava TP, Dube B (1975) Myopathy and neuropathy associated with osteomalacia. Acta Neurol Scand 51:37–58

    Article  PubMed  CAS  Google Scholar 

  20. Yoshikawa S, Nakamura T, Tanabe H, Imamura T (1979) Osteomalacic myopathy. Endocrinol Jpn 26:65–72

    Article  PubMed  CAS  Google Scholar 

  21. Palmucci L, Bertolotto A, Doriguzzi C, Mongini T, Coda R (1982) Osteomalacic myopathy in a case of diffuse nodular lipomatosis of the small bowel. Acta Neurol Belgica 82:65–71

    CAS  Google Scholar 

  22. McComas A (1996) Skeletal muscle. Form and function. Human Kinetics Publishers, Champaign

    Google Scholar 

  23. Gilsanz V, Kremer A, Mo AO, Wren TA, Kremer R (2010) Vitamin D status and its relation to muscle mass and muscle fat in young women. J Clin Endocrinol Metab 95:1595–1601

    Article  PubMed  CAS  Google Scholar 

  24. Lazaro RP, Kirshner HS (1980) Proximal muscle weakness in uremia. Case reports and review of the literature. Arch Neurol 37:555–558

    Article  PubMed  CAS  Google Scholar 

  25. Floyd M, Ayyar DR, Barwick DD, Hudgson P, Weightman D (1974) Myopathy in chronic renal failure. Q J Med 43:509–524

    PubMed  CAS  Google Scholar 

  26. Tague SE, Clarke GL, Winter MK, McCarson KE, Wright DE, Smith PG (2011) Vitamin D deficiency promotes skeletal muscle hypersensitivity and sensory hyperinnervation. J Neurosci 31:13728–13738

    Article  PubMed  CAS  Google Scholar 

  27. Sorensen OH, Lund B, Saltin B, Lund B, Andersen RB, Hjorth L, Melsen F, Mosekilde L (1979) Myopathy in bone loss of ageing: improvement by treatment with 1 alpha-hydroxycholecalciferol and calcium. Clin Sci (Lond) 56:157–161

    CAS  Google Scholar 

  28. Sato Y, Iwamoto J, Kanoko T, Satoh K (2005) Low-dose vitamin D prevents muscular atrophy and reduces falls and hip fractures in women after stroke: a randomized controlled trial. Cerebrovasc Dis 20:187–192

    Article  PubMed  CAS  Google Scholar 

  29. Bischoff-Ferrari HA, Dietrich T, Orav EJ, Hu FB, Zhang Y, Karlson EW, Dawson-Hughes B (2004) Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged > or = 60 y. Am J Clin Nutr 80:752–758

    PubMed  CAS  Google Scholar 

  30. Wicherts IS, van Schoor NM, Boeke AJ, Visser M, Deeg DJ, Smit J, Knol DL, Lips P (2007) Vitamin D status predicts physical performance and its decline in older persons. J Clin Endocrinol Metab 92:2058–2065

    Article  PubMed  CAS  Google Scholar 

  31. Kuchuk NO, Pluijm SM, van Schoor NM, Looman CW, Smit JH, Lips P (2009) Relationships of serum 25-hydroxyvitamin D to bone mineral density and serum parathyroid hormone and markers of bone turnover in older persons. J Clin Endocrinol Metab 94:1244–1250

    Article  PubMed  CAS  Google Scholar 

  32. Houston DK, Tooze JA, Davis CC, Chaves PH, Hirsch CH, Robbins JA, Arnold AM, Newman AB, Kritchevsky SB (2011) Serum 25-hydroxyvitamin D and physical function in older adults: the Cardiovascular Health Study All Stars. J Am Geriatr Soc 59:1793–1801

    Article  PubMed  Google Scholar 

  33. Chan R, Chan D, Woo J, Ohlsson C, Mellstrom D, Kwok T, Leung PC (2012) Not all elderly people benefit from vitamin D supplementation with respect to physical function: results from the Osteoporotic Fractures in Men Study, Hong Kong. J Am Geriatr Soc 60:290–295

    Article  PubMed  Google Scholar 

  34. Ceglia L, Chiu GR, Harris SS, Araujo AB (2011) Serum 25-hydroxyvitamin D concentration and physical function in adult men. Clin Endocrinol (Oxf) 74:370–376

    Article  CAS  Google Scholar 

  35. Ward KA, Das G, Berry JL, Roberts SA, Rawer R, Adams JE, Mughal Z (2009) Vitamin D status and muscle function in post-menarchal adolescent girls. J Clin Endocrinol Metab 94:559–563

    Article  PubMed  CAS  Google Scholar 

  36. Foo LH, Zhang Q, Zhu K, Ma G, Hu X, Greenfield H, Fraser DR (2009) Low vitamin D status has an adverse influence on bone mass, bone turnover, and muscle strength in Chinese adolescent girls. J Nutr 139:1002–1007

    Article  PubMed  CAS  Google Scholar 

  37. Allali F, El Aichaoui S, Khazani H, Benyahia B, Saoud B, El Kabbaj S, Bahiri R, Abouqal R, Hajjaj-Hassouni N (2009) High prevalence of hypovitaminosis D in Morocco: relationship to lifestyle, physical performance, bone markers, and bone mineral density. Semin Arthritis Rheum 38:444–451

    Article  PubMed  CAS  Google Scholar 

  38. Garnero P, Munoz F, Sornay-Rendu E, Delmas PD (2007) Associations of vitamin D status with bone mineral density, bone turnover, bone loss and fracture risk in healthy postmenopausal women. The OFELY study. Bone 40:716–722

    Article  PubMed  CAS  Google Scholar 

  39. Pfeifer M, Begerow B, Minne HW, Suppan K, Fahrleitner-Pammer A, Dobnig H (2009) Effects of a long-term vitamin D and calcium supplementation on falls and parameters of muscle function in community-dwelling older individuals. Osteoporos Int 20:315–322

    Article  PubMed  CAS  Google Scholar 

  40. Pfeifer M, Begerow B, Minne HW, Abrams C, Nachtigall D, Hansen C (2000) Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women. J Bone Miner Res 15:1113–1118

    Article  PubMed  CAS  Google Scholar 

  41. Bischoff HA, Stahelin HB, Dick W, Akos R, Knecht M, Salis C, Nebiker M, Theiler R, Pfeifer M, Begerow B, Lew RA, Conzelmann M (2003) Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res 18:343–351

    Article  PubMed  CAS  Google Scholar 

  42. Dhesi JK, Jackson SH, Bearne LM, Moniz C, Hurley MV, Swift CG, Allain TJ (2004) Vitamin D supplementation improves neuromuscular function in older people who fall. Age Ageing 33:589–595

    Article  PubMed  Google Scholar 

  43. Kenny AM, Biskup B, Robbins B, Marcella G, Burleson JA (2003) Effects of vitamin D supplementation on strength, physical function, and health perception in older, community-dwelling men. J Am Geriatr Soc 51:1762–1767

    Article  PubMed  Google Scholar 

  44. Latham NK, Anderson CS, Lee A, Bennett DA, Moseley A, Cameron ID (2003) A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people: the Frailty Interventions Trial in Elderly Subjects (FITNESS). J Am Geriatr Soc 51:291–299

    Article  PubMed  Google Scholar 

  45. Brunner RL, Cochrane B, Jackson RD, Larson J, Lewis C, Limacher M, Rosal M, Shumaker S, Wallace R (2008) Calcium, vitamin D supplementation, and physical function in the Women’s Health Initiative. J Am Diet Assoc 108:1472–1479

    Article  PubMed  Google Scholar 

  46. Lips P, Binkley N, Pfeifer M, Recker R, Samanta S, Cohn DA, Chandler J, Rosenberg E, Papanicolaou DA (2010) Once-weekly dose of 8400 IU vitamin D(3) compared with placebo: effects on neuromuscular function and tolerability in older adults with vitamin D insufficiency. Am J Clin Nutr 91:985–991

    Article  PubMed  CAS  Google Scholar 

  47. Stockton KA, Mengersen K, Paratz JD, Kandiah D, Bennell KL (2011) Effect of vitamin D supplementation on muscle strength: a systematic review and meta-analysis. Osteoporos Int 22:859–871

    PubMed  CAS  Google Scholar 

  48. Muir SW, Montero-Odasso M (2011) Effect of vitamin D supplementation on muscle strength, gait and balance in older adults: a systematic review and meta-analysis. J Am Geriatr Soc 59:2291–2300

    Article  PubMed  Google Scholar 

  49. Faulkner KA, Cauley JA, Zmuda JM, Landsittel DP, Newman AB, Studenski SA, Redfern MS, Ensrud KE, Fink HA, Lane NE, Nevitt MC (2006) Higher 1,25-dihydroxyvitamin D3 concentrations associated with lower fall rates in older community-dwelling women. Osteoporos Int 17:1318–1328

    Article  PubMed  CAS  Google Scholar 

  50. Suzuki T, Kwon J, Kim H, Shimada H, Yoshida Y, Iwasa H, Yoshida H (2008) Low serum 25-hydroxyvitamin D levels associated with falls among Japanese community-dwelling elderly. J Bone Miner Res 23:1309–1317

    Article  PubMed  CAS  Google Scholar 

  51. Flicker L, Mead K, MacInnis RJ, Nowson C, Scherer S, Stein MS, Thomasx J, Hopper JL, Wark JD (2003) Serum vitamin D and falls in older women in residential care in Australia. J Am Geriatr Soc 51:1533–1538

    Article  PubMed  Google Scholar 

  52. Stein MS, Wark JD, Scherer SC, Walton SL, Chick P, Di Carlantonio M, Zajac JD, Flicker L (1999) Falls relate to vitamin D and parathyroid hormone in an Australian nursing home and hostel. J Am Geriatr Soc 47:1195–1201

    PubMed  CAS  Google Scholar 

  53. Dhesi JK, Bearne LM, Moniz C, Hurley MV, Jackson SH, Swift CG, Allain TJ (2002) Neuromuscular and psychomotor function in elderly subjects who fall and the relationship with vitamin D status. J Bone Miner Res 17:891–897

    Article  PubMed  CAS  Google Scholar 

  54. Michael YL, Whitlock EP, Lin JS, Fu R, O’Connor EA, Gold R (2010) Primary care-relevant interventions to prevent falling in older adults: a systematic evidence review for the US Preventive Services Task Force. Ann Intern Med 153:815–825

    PubMed  Google Scholar 

  55. Murad MH, Elamin KB, Abu Elnour NO, Elamin MB, Alkatib AA, Fatourechi MM, Almandoz JP, Mullan RJ, Lane MA, Liu H, Erwin PJ, Hensrud DD, Montori VM (2011) Clinical review. The effect of vitamin D on falls: a systematic review and meta-analysis. J Clin Endocrinol Metab 96:2997–3006

    Article  PubMed  CAS  Google Scholar 

  56. 56. Gillespie LD, Robertson MC, Gillespie WJ, Lamb SE, Gates S, Cumming RG, Rowe BH (2009) Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev (2):CD007146

  57. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA (2011) The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 96:53–58

    Article  PubMed  CAS  Google Scholar 

  58. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, Orav JE, Stuck AE, Theiler R, Wong JB, Egli A, Kiel DP, Henschkowski J (2009) Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ (Clin Res Ed) 339:b3692

    Article  CAS  Google Scholar 

  59. Bischoff-Ferrari HA, Dawson-Hughes B, Platz A, Orav EJ, Stahelin HB, Willett WC, Can U, Egli A, Mueller NJ, Looser S, Bretscher B, Minder E, Vergopoulos A, Theiler R (2010) Effect of high-dosage cholecalciferol and extended physiotherapy on complications after hip fracture: a randomized controlled trial. Arch Intern Med 170:813–820

    Article  PubMed  CAS  Google Scholar 

  60. Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, Nicholson GC (2010) Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA 303:1815–1822

    Article  PubMed  CAS  Google Scholar 

  61. Rodman JS, Baker T (1978) Changes in the kinetics of muscle contraction in vitamin D–depleted rats. Kidney Int 13:189–193

    Article  PubMed  CAS  Google Scholar 

  62. Curry OB, Basten JF, Francis MJ, Smith R (1974) Calcium uptake by sarcoplasmic reticulum of muscle from vitamin D-deficient rabbits. Nature 249:83–84

    Article  PubMed  CAS  Google Scholar 

  63. Matthews C, Heimberg KW, Ritz E, Agostini B, Fritzsche J, Hasselbach W (1977) Effect of 1,25-dihydroxycholecalciferol on impaired calcium transport by the sarcoplasmic reticulum in experimental uremia. Kidney Int 11:227–235

    Article  PubMed  CAS  Google Scholar 

  64. Birge SJ, Haddad JG (1975) 25-Hydroxycholecalciferol stimulation of muscle metabolism. J Clin Invest 56:1100–1107

    Article  PubMed  CAS  Google Scholar 

  65. Costa EM, Blau HM, Feldman D (1986) 1,25-Dihydroxyvitamin D3 receptors and hormonal responses in cloned human skeletal muscle cells. Endocrinology 119:2214–2220

    Article  PubMed  CAS  Google Scholar 

  66. Ceglia L, da Silva Morais M, Park LK, Morris E, Harris SS, Bischoff-Ferrari HA, Fielding RA, Dawson-Hughes B (2010) Multi-step immunofluorescent analysis of vitamin D receptor loci and myosin heavy chain isoforms in human skeletal muscle. J Mol Histol 41:137–142

    Article  PubMed  CAS  Google Scholar 

  67. Srikuea R, Zhang X, Park-Sarge OK, Esser KA (2012) VDR and CYP27B1 are expressed in c2c12 cells and regenerating skeletal muscle: potential role in suppression of myoblast proliferation. Am J Physiol Cell Physiol 303:C396–C405

    Article  PubMed  CAS  Google Scholar 

  68. Dusso AS, Brown AJ, Slatopolsky E (2005) Vitamin D. Am J Physiol Renal Physiol 289:F8–F28

    Article  PubMed  CAS  Google Scholar 

  69. Pike JW (1991) Vitamin D3 receptors: structure and function in transcription. Annu Rev Nutr 11:189–216

    Article  PubMed  CAS  Google Scholar 

  70. Baker AR, McDonnell DP, Hughes M, Crisp TM, Mangelsdorf DJ, Haussler MR, Pike JW, Shine J, O’Malley BW (1988) Cloning and expression of full-length cDNA encoding human vitamin D receptor. Proc Natl Acad Sci USA 85:3294–3298

    Article  PubMed  CAS  Google Scholar 

  71. McDonnell DP, Mangelsdorf DJ, Pike JW, Haussler MR, O’Malley BW (1987) Molecular cloning of complementary DNA encoding the avian receptor for vitamin D. Science 235:1214–1217

    Article  PubMed  CAS  Google Scholar 

  72. DeLuca HF (1988) The vitamin D story: a collaborative effort of basic science and clinical medicine. FASEB J 2:224–236

    PubMed  CAS  Google Scholar 

  73. Haussler MR, Mangelsdorf DJ, Komm BS, Terpening CM, Yamaoka K, Allegretto EA, Baker AR, Shine J, McDonnell DP, Hughes M et al (1988) Molecular biology of the vitamin D hormone. Recent Prog Horm Res 44:263–305

    PubMed  CAS  Google Scholar 

  74. Mangelsdorf DJ, Ong ES, Dyck JA, Evans RM (1990) Nuclear receptor that identifies a novel retinoic acid response pathway. Nature 345:224–229

    Article  PubMed  CAS  Google Scholar 

  75. Nemere I, Farach-Carson MC (1998) Membrane receptors for steroid hormones: a case for specific cell surface binding sites for vitamin D metabolites and estrogens. Biochem Biophys Res Commun 248:443–449

    Article  PubMed  CAS  Google Scholar 

  76. Baran DT, Quail JM, Ray R, Leszyk J, Honeyman T (2000) Annexin II is the membrane receptor that mediates the rapid actions of 1alpha,25-dihydroxyvitamin D(3). J Cell Biochem 78:34–46

    Article  PubMed  CAS  Google Scholar 

  77. Capiati D, Benassati S, Boland RL (2002) 1,25(OH)2-Vitamin D3 induces translocation of the vitamin D receptor (VDR) to the plasma membrane in skeletal muscle cells. J Cell Biochem 86:128–135

    Article  PubMed  CAS  Google Scholar 

  78. Buitrago C, Boland R (2010) Caveolae and caveolin-1 are implicated in 1alpha,25(OH)(2)-vitamin D(3)-dependent modulation of Src, MAPK cascades and VDR localization in skeletal muscle cells. J Steroid Biochem Mol Biol 121:169–175

    Article  PubMed  CAS  Google Scholar 

  79. Simons K, Toomre D (2000) Lipid rafts and signal transduction. Nat Rev Mol Cell Biol 1:31–39

    Article  PubMed  CAS  Google Scholar 

  80. Galbiati F, Razani B, Lisanti MP (2001) Emerging themes in lipid rafts and caveolae. Cell 106:403–411

    Article  PubMed  CAS  Google Scholar 

  81. Boland R, Norman A, Ritz E, Hasselbach W (1985) Presence of a 1,25-dihydroxy-vitamin D3 receptor in chick skeletal muscle myoblasts. Biochem Biophys Res Commun 128:305–311

    Article  PubMed  CAS  Google Scholar 

  82. Wang Y, DeLuca HF (2011) Is the vitamin D receptor found in muscle? Endocrinology 152:354–363

    Article  PubMed  CAS  Google Scholar 

  83. Ceglia LMM, Park L, Harris S, Bischoff-Ferrari H, Fielding RA, Dawson-Hughes B (2008) Immunofluorescent analysis of vitamin D receptor loci and myosin heavy chain isoforms in human skeletal muscle fibers. Osteoporos Int 19(suppl 2):S418

    Google Scholar 

  84. Endo I, Inoue D, Mitsui T, Umaki Y, Akaike M, Yoshizawa T, Kato S, Matsumoto T (2003) Deletion of vitamin D receptor gene in mice results in abnormal skeletal muscle development with deregulated expression of myoregulatory transcription factors. Endocrinology 144:5138–5144

    Article  PubMed  CAS  Google Scholar 

  85. Burne TH, McGrath JJ, Eyles DW, Mackay-Sim A (2005) Behavioural characterization of vitamin D receptor knockout mice. Behav Brain Res 157:299–308

    Article  PubMed  CAS  Google Scholar 

  86. Song Y, Kato S, Fleet JC (2003) Vitamin D receptor (VDR) knockout mice reveal VDR-independent regulation of intestinal calcium absorption and ECaC2 and calbindin D9k mRNA. J Nutr 133:374–380

    PubMed  CAS  Google Scholar 

  87. Kalueff AV, Lou YR, Laaksi I, Tuohimaa P (2004) Impaired motor performance in mice lacking neurosteroid vitamin D receptors. Brain Res Bull 64:25–29

    Article  PubMed  CAS  Google Scholar 

  88. Minasyan A, Keisala T, Zou J, Zhang Y, Toppila E, Syvala H, Lou YR, Kalueff AV, Pyykko I, Tuohimaa P (2009) Vestibular dysfunction in vitamin D receptor mutant mice. J Steroid Biochem Mol Biol 114:161–166

    Article  PubMed  CAS  Google Scholar 

  89. Boland R, de Boland AR, Marinissen MJ, Santillan G, Vazquez G, Zanello S (1995) Avian muscle cells as targets for the secosteroid hormone 1,25-dihydroxy-vitamin D3. Mol Cell Endocrinol 114:1–8

    Article  PubMed  CAS  Google Scholar 

  90. Ebashi S, Endo M (1968) Calcium ion and muscle contraction. Prog Biophys Mol Biol 18:123–183

    Article  PubMed  CAS  Google Scholar 

  91. Lila D, Susana Z, Ricardo B (1994) Induction of a calbindin-D9K-like protein in avian muscle cells by 1,25-dihydroxy-vitamin D3. Biochem Mol Biol Int 32:859–867

    PubMed  CAS  Google Scholar 

  92. Drittanti LN, Boland RL, de Boland AR (1989) Induction of specific proteins in cultured skeletal muscle cells by 1,25-dihydroxyvitamin D-3. Biochim Biophys Acta 1012:16–23

    Article  PubMed  CAS  Google Scholar 

  93. Zanello SB, Boland RL, Norman AW (1995) cDNA sequence identity of a vitamin D-dependent calcium-binding protein in the chick to calbindin D-9K. Endocrinology 136:2784–2787

    Article  PubMed  CAS  Google Scholar 

  94. Brunner A, de Boland AR (1990) 1,25-Dihydroxyvitamin D3 affects the synthesis, phosphorylation and in vitro calmodulin binding of myoblast cytoskeletal proteins. Z Naturforsch C 45:1156–1160

    PubMed  CAS  Google Scholar 

  95. Drittanti L, de Boland AR, Boland R (1990) Stimulation of calmodulin synthesis in proliferating myoblasts by 1,25-dihydroxy-vitamin D3. Mol Cell Endocrinol 74:143–153

    Article  PubMed  CAS  Google Scholar 

  96. Bellido T, Boland R (1991) Effects of 1,25-dihydroxy-vitamin D3 on phosphate accumulation by myoblasts. Horm Metab Res 23:113–116

    Article  PubMed  CAS  Google Scholar 

  97. Inoue Y, Segawa H, Kaneko I, Yamanaka S, Kusano K, Kawakami E, Furutani J, Ito M, Kuwahata M, Saito H, Fukushima N, Kato S, Kanayama HO, Miyamoto K (2005) Role of the vitamin D receptor in FGF23 action on phosphate metabolism. Biochem J 390:325–331

    Article  PubMed  CAS  Google Scholar 

  98. Giuliani DL, Boland RL (1984) Effects of vitamin D3 metabolites on calcium fluxes in intact chicken skeletal muscle and myoblasts cultured in vitro. Calcif Tissue Int 36:200–205

    Article  PubMed  CAS  Google Scholar 

  99. Drittanti L, de Boland AR, Boland R (1989) Modulation of DNA synthesis in cultured muscle cells by 1,25-dihydroxyvitamin D-3. Biochim Biophys Acta 1014:112–119

    Article  PubMed  CAS  Google Scholar 

  100. Garcia LA, King KK, Ferrini MG, Norris KC, Artaza JN (2011) 1,25(OH)2 Vitamin D3 stimulates myogenic differentiation by inhibiting cell proliferation and modulating the expression of promyogenic growth factors and myostatin in C2C12 skeletal muscle cells. Endocrinology 152:2976–2986

    Article  PubMed  CAS  Google Scholar 

  101. Dirks-Naylor AJ, Lennon-Edwards S (2011) The effects of vitamin D on skeletal muscle function and cellular signaling. J Steroid Biochem Mol Biol 125:159–168

    Article  PubMed  CAS  Google Scholar 

  102. Williams TM, Lisanti MP (2004) The Caveolin genes: from cell biology to medicine. Ann Med 36:584–595

    Article  PubMed  CAS  Google Scholar 

  103. Buitrago C, Arango N, Boland R (2012) 1alpha,25(OH)(2)D(3)-dependent modulation of Akt in proliferating and differentiating C2C12 skeletal muscle cells. J Cell Biochem 113:1170–1181

    Article  PubMed  CAS  Google Scholar 

  104. Zhang X, Zanello LP (2008) Vitamin D receptor-dependent 1 alpha,25(OH)2 vitamin D3–induced anti-apoptotic PI3K/AKT signaling in osteoblasts. J Bone Miner Res 23:1238–1248

    Article  PubMed  CAS  Google Scholar 

  105. Selles J, Boland R (1991) Rapid stimulation of calcium uptake and protein phosphorylation in isolated cardiac muscle by 1,25-dihydroxyvitamin D3. Mol Cell Endocrinol 77:67–73

    Article  PubMed  CAS  Google Scholar 

  106. de Boland AR, Boland RL (1987) Rapid changes in skeletal muscle calcium uptake induced in vitro by 1,25-dihydroxyvitamin D3 are suppressed by calcium channel blockers. Endocrinology 120:1858–1864

    Article  PubMed  Google Scholar 

  107. Morelli S, Boland R, de Boland AR (1996) 1,25(OH)2-vitamin D3 stimulation of phospholipases C and D in muscle cells involves extracellular calcium and a pertussis-sensitive G protein. Mol Cell Endocrinol 122:207–211

    Article  PubMed  CAS  Google Scholar 

  108. Vazquez G, Boland R, de Boland AR (1995) Modulation by 1,25(OH)2-vitamin D3 of the adenylyl cyclase/cyclic AMP pathway in rat and chick myoblasts. Biochim Biophys Acta 1269:91–97

    Article  PubMed  Google Scholar 

  109. Capiati DA, Vazquez G, Tellez Inon MT, Boland RL (2000) Role of protein kinase C in 1,25(OH)(2)-vitamin D(3) modulation of intracellular calcium during development of skeletal muscle cells in culture. J Cell Biochem 77:200–212

    Article  PubMed  CAS  Google Scholar 

  110. Vazquez G, de Boland AR, Boland RL (1997) 1 alpha,25-(OH)2-Vitamin D3 stimulates the adenylyl cyclase pathway in muscle cells by a GTP-dependent mechanism which presumably involves phosphorylation of G alpha i. Biochem Biophys Res Commun 234:125–128

    Article  PubMed  CAS  Google Scholar 

  111. Vazquez G, de Boland AR (1996) Involvement of protein kinase C in the modulation of 1alpha,25-dihydroxy-vitamin D3-induced 45Ca2+ uptake in rat and chick cultured myoblasts. Biochim Biophys Acta 1310:157–162

    Article  PubMed  Google Scholar 

  112. Vazquez G, de Boland AR, Boland R (1997) Stimulation of Ca2+ release-activated Ca2+ channels as a potential mechanism involved in non-genomic 1,25(OH)2-vitamin D3-induced Ca2+ entry in skeletal muscle cells. Biochem Biophys Res Commun 239:562–565

    Article  PubMed  CAS  Google Scholar 

  113. Vazquez G, de Boland AR, Boland RL (1998) 1alpha,25-Dihydroxy-vitamin-D3-induced store-operated Ca2+ influx in skeletal muscle cells. Modulation by phospholipase c, protein kinase c, and tyrosine kinases. J Biol Chem 273:33954–33960

    Article  PubMed  CAS  Google Scholar 

  114. Vazquez G, de Boland AR (1993) Stimulation of dihydropyridine-sensitive Ca2+ influx in cultured myoblasts by 1,25(OH)2-vitamin D3. Biochem Mol Biol Int 31:677–684

    PubMed  CAS  Google Scholar 

  115. Nejentsev S, Godfrey L, Snook H, Rance H, Nutland S, Walker NM, Lam AC, Guja C, Ionescu-Tirgoviste C, Undlien DE, Ronningen KS, Tuomilehto-Wolf E, Tuomilehto J, Newport MJ, Clayton DG, Todd JA (2004) Comparative high-resolution analysis of linkage disequilibrium and tag single nucleotide polymorphisms between populations in the vitamin D receptor gene. Hum Mol Genet 13:1633–1639

    Article  PubMed  CAS  Google Scholar 

  116. Arai H, Miyamoto K, Taketani Y, Yamamoto H, Iemori Y, Morita K, Tonai T, Nishisho T, Mori S, Takeda E (1997) A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women. J Bone Miner Res 12:915–921

    Article  PubMed  CAS  Google Scholar 

  117. Whitfield GK, Remus LS, Jurutka PW, Zitzer H, Oza AK, Dang HT, Haussler CA, Galligan MA, Thatcher ML, Encinas Dominguez C, Haussler MR (2001) Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene. Mol Cell Endocrinol 177:145–159

    Article  PubMed  CAS  Google Scholar 

  118. Roth SM, Zmuda JM, Cauley JA, Shea PR, Ferrell RE (2004) Vitamin D receptor genotype is associated with fat-free mass and sarcopenia in elderly men. J Gerontol 59:10–15

    Article  Google Scholar 

  119. Windelinckx A, De Mars G, Beunen G, Aerssens J, Delecluse C, Lefevre J, Thomis MA (2007) Polymorphisms in the vitamin D receptor gene are associated with muscle strength in men and women. Osteoporos Int 18:1235–1242

    Article  PubMed  CAS  Google Scholar 

  120. Hopkinson NS, Li KW, Kehoe A, Humphries SE, Roughton M, Moxham J, Montgomery H, Polkey MI (2008) Vitamin D receptor genotypes influence quadriceps strength in chronic obstructive pulmonary disease. Am J Clin Nutr 87:385–390

    PubMed  CAS  Google Scholar 

  121. Geusens P, Vandevyver C, Vanhoof J, Cassiman JJ, Boonen S, Raus J (1997) Quadriceps and grip strength are related to vitamin D receptor genotype in elderly nonobese women. J Bone Miner Res 12:2082–2088

    Article  PubMed  CAS  Google Scholar 

  122. Onder G, Capoluongo E, Danese P, Settanni S, Russo A, Concolino P, Bernabei R, Landi F (2008) Vitamin D receptor polymorphisms and falls among older adults living in the community: results from the ilSIRENTE study. J Bone Miner Res 23:1031–1036

    Article  PubMed  CAS  Google Scholar 

  123. Barr R, Macdonald H, Stewart A, McGuigan F, Rogers A, Eastell R, Felsenberg D, Gluer C, Roux C, Reid DM (2010) Association between vitamin D receptor gene polymorphisms, falls, balance and muscle power: results from two independent studies (APOSS and OPUS). Osteoporos Int 21:457–466

    Article  PubMed  CAS  Google Scholar 

  124. Grundberg E, Brandstrom H, Ribom EL, Ljunggren O, Mallmin H, Kindmark A (2004) Genetic variation in the human vitamin D receptor is associated with muscle strength, fat mass and body weight in Swedish women. Eur J Endocrinol 150:323–328

    Article  PubMed  CAS  Google Scholar 

  125. Bahat G, Saka B, Erten N, Ozbek U, Coskunpinar E, Yildiz S, Sahinkaya T, Karan MA (2010) BsmI polymorphism in the vitamin D receptor gene is associated with leg extensor muscle strength in elderly men. Aging Clin Exp Res 22:198–205

    PubMed  CAS  Google Scholar 

  126. Zehnder D, Bland R, Walker EA, Bradwell AR, Howie AJ, Hewison M, Stewart PM (1999) Expression of 25-hydroxyvitamin D3-1alpha-hydroxylase in the human kidney. J Am Soc Nephrol 10:2465–2473

    PubMed  CAS  Google Scholar 

  127. Choudhary D, Jansson I, Schenkman JB, Sarfarazi M, Stoilov I (2003) Comparative expression profiling of 40 mouse cytochrome P450 genes in embryonic and adult tissues. Arch Biochem Biophys 414:91–100

    Article  PubMed  CAS  Google Scholar 

  128. Zehnder D, Bland R, Williams MC, McNinch RW, Howie AJ, Stewart PM, Hewison M (2001) Extrarenal expression of 25-hydroxyvitamin D(3)-1 alpha-hydroxylase. J Clin Endocrinol Metab 86:888–894

    Article  PubMed  CAS  Google Scholar 

  129. Lou YR, Molnar F, Perakyla M, Qiao S, Kalueff AV, St-Arnaud R, Carlberg C, Tuohimaa P (2010) 25-Hydroxyvitamin D(3) is an agonistic vitamin D receptor ligand. J Steroid Biochem Mol Biol 118:162–170

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This material is based upon work supported by the U.S. Department of Agriculture, Agricultural Research Service, under agreement No. 58-1950-7-707. Any opinions, findings, conclusion, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture.

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  1. Division of Endocrinology, Diabetes, and Metabolism, Tufts Medical Center, 800 Washington Street, Box 268, Boston, MA, 02111, USA

    Lisa Ceglia

  2. Bone Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, 02111, USA

    Lisa Ceglia & Susan S. Harris

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  1. Lisa Ceglia
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Correspondence to Lisa Ceglia.

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Ceglia, L., Harris, S.S. Vitamin D and Its Role in Skeletal Muscle. Calcif Tissue Int 92, 151–162 (2013). https://doi.org/10.1007/s00223-012-9645-y

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