Mechanisms of vitamin D action in skeletal muscle – June 2019

Nutrition Research Reviews doi:10.1017/S0954422419000064
Karina Romeu Montenegro1, Vinicius Cruzat1,2, Rodrigo Carlessi1 and Philip Newsholme1
1School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA6102, Australia
2Faculty of Health, Torrens University Australia, Melbourne, VIC 3065, Australia

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Muscle tissue including cell

Note: Receptor appears 3 times in tissue and 2 times in cell

Chart Caption
Proposed mechanisms of action of vitamin D (VitD) in mammalian skeletal muscle cells. 4E-BP1, eukaryotic translation initiation factor 4E-binding protein 1; AKT, serine–threonine kinase; Ca2þ, calcium ions; CREB, cellular transcription factor; c-Src, proto-oncogene c-Src; DAG, diacylglycerol; ELK1, ETS domain-containing protein; ERK1/2, extracellular signal-regulated kinases; HSP27, heat shock protein 27; IP3, inositol triphosphate; MAPK, mitogen-activated protein kinase; mTOR, mammalian target of rapamycin; OCR, oxygen consumption rate; P38, P38 mitogen-activated protein kinases; P70S6K, ribosomal protein S6 kinase β-1; PI3K, phosphoinositide-3 kinase; PIP2, phosphatidylinositol biphosphate; PKC, protein kinase C; PLCγ, phospholipase Cγ; Raf-1, proto-oncogene serine/threonine-protein kinase (also known as c-RAF); RNA poly, RNA polymerase; RXR, retinoid X receptor; SOCE, store-operated calcium entry; SR, sarcoplasmic reticulum; VDCC, L-type voltage-dependent calcium channel; VDR, vitamin D receptor; VDRE, vitamin D response elements.

Abstract
Vitamin D receptor expression and associated function have been reported in various muscle models, including C2C12, L6 cell lines and primary human skeletal muscle cells. It is believed that 1,25-hydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D, has a direct regulatory role in skeletal muscle function, where it participates in myogenesis, cell proliferation, differentiation, regulation of protein synthesis and mitochondrial metabolism through activation of various cellular signalling cascades, including the mitogen-activated protein kinase pathway(s). It has also been suggested that 1,25(OH)2D3 and its associated receptor have genomic targets, resulting in regulation of gene expression, as well as non-genomic functions that can alter cellular behaviour through binding and modification of targets not directly associated with transcriptional regulation. The molecular mechanisms of vitamin D signalling, however, have not been fully clarified. Vitamin D inadequacy or deficiency is associated with muscle fibre atrophy, increased risk of chronic musculoskeletal pain, sarcopenia and associated falls, and may also decrease RMR. The main purpose of the present review is to describe the molecular role of vitamin D in skeletal muscle tissue function and metabolism, specifically in relation to proliferation, differentiation and protein synthesis processes. In addition, the present review also includes discussion of possible genomic and non-genomic pathways of vitamin D action.

References

1. Bikle DD (2011) Vitamin D: an ancient hormone. Exp Dermatol 20, 7-13.
2. Wacker M & Holick MF (2013) Vitamin D- effects on skeletal and extraskeletal health and the need for supplementation. Nutrients 5, 111-148.
3. Heath KM & Elovic EP (2006) Vitamin D deficiency: implications in the rehabilitation setting. Am J Phys Med Rehabil 85, 916-923.
4. Gendelman O, Itzhaki D, Makarov S, et al. (2015) A randomized double-blind placebo-controlled study adding high dose vitamin D to analgesic regimens in patients with musculoskeletal pain. Lupus 24, 483-489.
5. Daly RM, Gagnon C, Lu ZX, etal. (2012) Prevalence of vitamin D deficiency and its determinants in Australian adults aged 25 years and older: a national, population-based study. Clin Endocrinol (Oxf) 77, 26-35.
6. Girgis CM, Clifton-Bligh RJ, Turner N, et al. (2014) Effects of vitamin D in skeletal muscle: falls, strength, athletic performance and insulin sensitivity. Clin Endocrinol (Oxf) 80, 169-181.
7. Chowdhury R, Kunutsor S, Vitezova A, et al. (2014) Vitamin D and risk of cause specific death: systematic review and metaanalysis of observational cohort and randomised intervention studies. BMJ348, g1903.
8. Pfotenhauer KM & Shubrook JH (2017) Vitamin D deficiency, its role in health and disease, and current supplementation recommendations. JAm Osteopath Assoc 117, 301-305.
9. Herrmann M, Sullivan DR, Veillard AS, et al. (2015) Serum 25-hydroxyvitamin D: a predictor of macrovascular and microvascular complications in patients with type 2 diabetes. Diabetes Care 38, 521-528.
10. Calton EK, Keane KN, Newsholme P, et al. (2015) The impact of vitamin D levels on inflammatory status: a systematic review of immune cell studies. PLOS ONE 10, e0141770.
11. Hassan-Smith ZK, Jenkinson C, Smith DJ, et al. (2017) 25-Hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 exert distinct effects on human skeletal muscle function and gene expression. PLOS ONE 12, e0170665.
12. Simpson RU, Thomas GA & Arnold AJ (1985) Identification of 1,25-dihydroxyvitamin D3 receptors and activities in muscle. J Biol Chem 260, 8882-8891.
13. Antinozzi C, Corinaldesi C, Giordano C, et al. (2017) Potential role for the VDR agonist elocalcitol in metabolic control: evidences in human skeletal muscle cells. J Steroid Biochem Mol Biol 167, 169-181.
14. Pojednic RM, Ceglia L, Olsson K, et al. (2015) Effects of 1, 25-dihydroxyvitamin D3 and vitamin D3 on the expression of the vitamin D receptor in human skeletal muscle cells. Calcif Tissue Int 96, 256-263.
15. Pfeifer M, Begerow B & Minne HW (2002) Vitamin D and muscle function. Osteoporos Int 13, 187-194.
16. Campbell PM & Allain TJ (2006) Muscle strength and vitamin D in older people. Gerontology 52, 335-338.
17. Ceglia L (2008) Vitamin D and skeletal muscle tissue and function. Mol Aspects Med 29, 407-414.
18. Lappe J, Cullen D, Haynatzki G, et al. (2008) Calcium and vitamin D supplementation decreases incidence of stress fractures in female navy recruits. J Bone Miner Res 23, 741-749.
19. Dahlquist DT, Dieter BP & Koehle MS (2015) Plausible ergogenic effects of vitamin D on athletic performance and recovery. J Int Soc Sports Nutr 12, 33.
20. Bergman P, Lindh AU, Bjorkhem-Bergman L, et al. (2013) Vitamin D and respiratory tract infections: a systematic review and meta-analysis of randomized controlled trials. PLOS ONE 8, e65835.
21. Chiang CM, Ismaeel A, Griffis RB, et al. (2017) Effects of vitamin D supplementation on muscle strength in athletes: a systematic review. J Strength Cond Res 31, 566-574.
22. SalminenM, Saaristo P, SalonojaM, etal. (2015) Vitamin D status and physical function in older Finnish people: a one-year follow-up study. Arch Gerontol Geriatr 61, 419-424.
23. Olsson K, Saini A, Stromberg A, etal. (2016) Evidence for vitamin D receptor expression and direct effects of 1a,25(OH)2D3 in human skeletal muscle precursor cells. Endocrinology 157, 98-111.
24. Ryan ZC, Craig TA, Folmes CD, et al. (2016) 1a, 25-Dihydroxyvitamin D3 regulates mitochondrial oxygen consumption and dynamics in human skeletal muscle cells. J Biol Chem 291, 1514-1528.
25. Owens DJ, Sharples AP, Polydorou I, et al. (2015) A systems- based investigation into vitamin D and skeletal muscle repair, regeneration, and hypertrophy. Am J Physiol Endocrinol Metab 309, E1019-E1031.
26. Calton EK, Pathak K, Soares MJ, et al. (2016) Vitamin D status and insulin sensitivity are novel predictors of resting metabolic rate: a cross-sectional analysis in Australian adults. EurJNutr 55, 2075-2080.
27. Chen TC, Chimeh F, Lu ZR, et al. (2007) Factors that influence the cutaneous synthesis and dietary sources of vitamin D. Arch Biochem Biophys 460, 213-217.
28. Armas LA, Hollis BW & Heaney RP (2004) Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab 89, 5387-5391.
29. Heaney RP & Holick MF (2011) Why the IOM recommendations for vitamin D are deficient. J Bone Miner Res 26, 455-457.
30. Girgis CM, Clifton-Bligh RJ, Hamrick MW, et al. (2013) The roles of vitamin D in skeletal muscle: form, function, and metabolism. Endocr Rev 34, 33-83.
31. Norman AW, Nemere I, Zhou LX, et al. (1992) 1,25(OH)2- vitamin D3, a steroid hormone that produces biologic effects via both genomic and nongenomic pathways. J Steroid Biochem Mol Biol 41, 231-240.
32. Chun RF, Peercy BE, Orwoll ES, et al. (2014) Vitamin D and DBP: the free hormone hypothesis revisited. J Steroid Biochem Mol Biol 144, 132-137.
33. Tsuprykov O, Chen X, Hocher CF, et al. (2018) Why should we measure free 25(OH) vitamin D? J Steroid Biochem Mol Biol 180, 87-104.
34. Powe CE, Evans MK, Wenger J, etal. (2013) Vitamin D-binding protein and vitamin D status of black Americans and white Americans. N Engl J Med 369, 1991-2000.
35. Bikle DD, Gee E, Halloran B, et al. (1986) Assessment of the free fraction of 25-hydroxyvitamin-D in serum and its regulation by albumin and the vitamin-D-binding protein. J Clin Endocr Metab 63, 954-959.
36. Powe CE, Ricciardi C, Berg AH, et al. (2011) Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res 26, 1609-1616.
37. Shieh A, Chun RF, Ma C, et al. (2016) Effects of high-dose vitamin D2 versus D3 on total and free 25-hydroxyvitamin D and markers of calcium balance. J Clin Endocrinol Metab 101, 3070-3078.
38. Allison RJ, Farooq A, Cherif A, et al. (2018) Why don’t serum vitamin D concentrations associate with BMD by DXA? A case of being ‘bound’ to the wrong assay? Implications for vitamin D screening.Br J Sports Med 52, 522-526.
39. Tajbakhsh S (2009) Skeletal muscle stem cells in developmental versus regenerative myogenesis. J Intern Med 266, 372-389.
40. Sambasivan R & Tajbakhsh S (2007) Skeletal muscle stem cell birth and properties. Semin Cell Dev Biol 18, 870-882.
41. Braun T & Gautel M (2011) Transcriptional mechanisms regulating skeletal muscle differentiation, growth and homeostasis. Nat Rev Mol Cell Biol 12, 349-361.
42. Bentzinger CF, Wang YX & Rudnicki MA (2012) Building muscle: molecular regulation of myogenesis. Cold Spring Harb Perspect Biol 4, a008342.
43. Pownall ME, Gustafsson MK & Emerson CP Jr (2002) Myogenic regulatory factors and the specification of muscle progenitors in vertebrate embryos. Annu Rev Cell Dev Biol 18, 747-783.
44. Berkes CA & Tapscott SJ (2005) MyoD and the transcriptional control of myogenesis. Semin Cell Dev Biol 16, 585-595.
45. Valdez MR, Richardson JA, Klein WH, et al. (2000) Failure of Myf5 to support myogenic differentiation without myogenin, MyoD, and MRF4. Dev Biol 219, 287-298.
46. Domingues-Faria C, Chanet A, Salles J, et al. (2014) Vitamin D deficiency down-regulates Notch pathway contributing to skeletal muscle atrophy in old Wistar rats. Nutr Metab (Lond) 11, 47.
47. Hutton KC, Vaughn MA, Litta G, et al. (2014) Effect of vitamin D status improvement with 25-hydroxycholecalciferol on skeletal muscle growth characteristics and satellite cell activity in broiler chickens. JAnim Sci 92, 3291-3299.
48. Girgis CM, Clifton-Bligh RJ, Mokbel N, et al. (2014) Vitamin D signaling regulates proliferation, differentiation, and myotube size in C2C12 skeletal muscle cells. Endocrinology 155, 347-357.
49. Bischoff HA, Borchers M, Gudat F, et al. (2001) In situ detection of 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle tissue. In situ 33, 19-24.
50. Bischoff-Ferrari HA, Borchers M, Gudat F, etal. (2004) Vitamin D receptor expression in human muscle tissue decreases with age. J Bone Miner Res 19, 265-269.
51. Ceglia L, da Silva Morais M, Park LK, et al. (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.
52. Girgis CM, Mokbel N, Cha KM, et al. (2014) The vitamin D receptor (VDR) is expressed in skeletal muscle of male mice and modulates 25-hydroxyvitamin D (25OHD) uptake in myofibers. Endocrinology 155, 3227-3237.
53. Oku Y, Tanabe R, Nakaoka K, et al. (2016) Influences of dietary vitamin D restriction on bone strength, body composition and muscle in rats fed a high-fat diet: involvement of mRNA expression of MyoD in skeletal muscle. J Nutr Biochem 32, 85-90.
54. Ray AD, Personius KE, Williamson DL, etal. (2016) Vitamin D3 intake modulates diaphragm but not peripheral muscle force in young mice. JApplPhysiol (1985) 120, 1124-1131.
55. Girgis CM, Cha KM, Houweling PJ, et al. (2015) Vitamin D receptor ablation and vitamin D deficiency result in reduced grip strength, altered muscle fibers, and increased myostatin in mice. Calcif Tissue Int 97, 602-610.
56. Garcia LA, King KK, Ferrini MG, et al. (2011)
57. 1,25(OH)2vitamin 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.
58. Srikuea R, Zhang X, Park-Sarge OK, et al. (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.
59. Garcia LA, Ferrini MG, Norris KC, et al. (2013)
60. 1,25(OH)2vitamin D3 enhances myogenic differentiation by modulating the expression of key angiogenic growth factors and angiogenic inhibitors in C2C12 skeletal muscle cells. J Steroid Biochem Mol Biol 133, 1-11.
61. Van der Meijden K, Bravenboer N, Dirks NF, et al. (2016) Effects of 1,25(OH)2D3 and 25(OH)D3 on C2C12 myoblast proliferation, differentiation, and myotube hypertrophy. J Cell Physiol 231, 2517-2528.
62. Irazoqui AP, Boland RL & Buitrago CG (2014) Actions of 1,25(OH)2-vitamin D3 on the cellular cycle depend on VDR and p38 MAPK in skeletal muscle cells. J Mol Endocrinol 53, 331-343.
63. Braga M, Simmons Z, Norris KC, et al. (2017) Vitamin D induces myogenic differentiation in skeletal muscle derived stem cells. Endocr Connect 6, 139-150.
64. Ryan KJ, Daniel ZC, Craggs LJ, et al. (2013) Dose-dependent effects of vitamin D on transdifferentiation of skeletal muscle cells to adipose cells. JEndocrinol 217, 45-58.
65. Goodpaster BH, Krishnaswami S, Resnick H, et al. (2003) Association between regional adipose tissue distribution and both type 2 diabetes and impaired glucose tolerance in elderly men and women. Diabetes Care 26, 372-379.
66. Hilton TN, Tuttle LJ, Bohnert KL, et al. (2008) Excessive adipose tissue infiltration in skeletal muscle in individuals with obesity, diabetes mellitus, and peripheral neuropathy: association with performance and function. Phys Ther 88, 1336-1344.
67. Zoico E, Rossi A, Di Francesco V, et al. (2010) Adipose tissue infiltration in skeletal muscle of healthy elderly men: relationships with body composition, insulin resistance, and inflammation at the systemic and tissue level. J Gerontol A Biol Sci Med Sci 65, 295-299.
68. Matsakas A & Patel K (2009) Intracellular signalling pathways regulating the adaptation of skeletal muscle to exercise and nutritional changes. Histol Histopathol 24, 209-222.
69. Trendelenburg AU, Meyer A, Rohner D, etal. (2009) Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size. Am J Physiol Cell Physiol 296, C1258-C1270.
70. Hay N & Sonenberg N (2004) Upstream and downstream of mTOR. Genes Dev 18, 1926-1945.
71. Winbanks CE, Weeks KL, Thomson RE, et al. (2012) Follistatin-mediated skeletal muscle hypertrophy is regulated by Smad3 and mTOR independently of myostatin. J Cell Biol 197, 997-1008.
72. Artaza JN & Norris KC (2009) Vitamin D reduces the expression of collagen and key profibrotic factors by inducing an antifibrotic phenotype in mesenchymal multipotent cells. J Endocrinol 200, 207-221.
73. Birge SJ & Haddad JG (1975) 25-Hydroxycholecalciferol stimulation of muscle metabolism. J Clin Invest 56, 11001107.
74. Salles J, Chanet A, GiraudetC, etal. (2013) 1,25(OH)2-vitamin D3 enhances the stimulating effect of leucine and insulin on protein synthesis rate through Akt/PKB and mTOR mediated pathways in murine C2C12 skeletal myotubes. Mol Nutr Food Res 57, 2137-2146.
75. Bolster DR, Jefferson LS & Kimball SR (2004) Regulation of protein synthesis associated with skeletal muscle hypertrophy by insulin-, amino acid- and exercise-induced signalling. Proc Nutr Soc 63, 351-356.
76. Proud CG & Denton RM (1997) Molecular mechanisms for the control of translation by insulin. Biochem J 328, 329-341.
77. Bhat M, Kalam R, Qadri SS, et al. (2013) Vitamin D deficiency- induced muscle wasting occurs through the ubiquitin protea- some pathway and is partially corrected by calcium in male rats. Endocrinology 154, 4018-4029.
78. Mitch WE & Goldberg AL (1996) Mechanisms of muscle wasting. The role of the ubiquitin-proteasome pathway. NEngl J Med 335, 1897-1905.
79. Bhat M & Ismail A (2015) Vitamin D treatment protects against and reverses oxidative stress induced muscle proteolysis. J Steroid Biochem Mol Biol 152, 171-179.
80. Bruyere O, Cavalier E, Souberbielle JC, et al. (2014) Effects of vitamin D in the elderly population: current status and perspectives. Arch Public Health 72, 32.
81. Deepa SS, Bhaskaran S, Ranjit R, et al. (2016) Down-regulation of the mitochondrial matrix peptidase ClpP in muscle cells causes mitochondrial dysfunction and decreases cell proliferation. Free Radic Biol Med 91, 281-292.
82. Sinha A, Hollingsworth KG, Ball S, et al. (2013) Improving the vitamin D status of vitamin D deficient adults is associated with improved mitochondrial oxidative function in skeletal muscle. J Clin Endocrinol Metab 98, E509-E513.
83. RanaP,Marwaha RK, Kumar P, etal. (2014) Effect of vitamin D supplementation on muscle energy phospho-metabolites: a 31P magnetic resonance spectroscopy-based pilot study. Endocr Res 39, 152-156.
84. Boon N, Hul GB, Sicard A, et al. (2006) The effects of increasing serum calcitriol on energy and fat metabolism and gene expression. Obesity (Silver Spring) 14, 1739-1746.
85. Silvagno F & Pescarmona G (2017) Spotlight on vitamin D receptor, lipid metabolism and mitochondria: some preliminary emerging issues. Mol Cell Endocrinol 450, 24-31.
86. Munoz Garcia A, Kutmon M, Eijssen L, et al. (2018) Pathway analysis of transcriptomic data shows immunometabolic effects of vitamin D. J Mol Endocrinol 60, 95-108.
87. Calton EK, Keane KN, Soares MJ, et al. (2016) Prevailing vitamin D status influences mitochondrial and glycolytic bioenergetics in peripheral blood mononuclear cells obtained from adults. Redox Biol 10, 243-250.
88. Pramono A, Jocken JWE & Blaak EE (2019) Vitamin D deficiency in the etiology of obesity related insulin resistance. Diabetes Metab Res Rev 2019, e3146.
89. Rudolf R, Mongillo M, Magalhaes PJ, et al. (2004) In vivo monitoring of Ca2+ uptake into mitochondria of mouse skeletal muscle during contraction. J Cell Biol 166, 527-536.
90. Mukherjee A, Zerwekh JE, Nicar MJ, et al. (1981) Effect of chronic vitamin D deficiency on chick heart mitochondrial oxidative phosphorylation./Mol Cell Cardiol 13, 171-183.
91. Hii CS & Ferrante A (2016) The non-genomic actions of vitamin D. Nutrients 8, 135.
92. Bouillon R, Gielen E & Vanderschueren D (2014) Vitamin D receptor and vitamin D action in muscle. Endocrinology 155, 3210-3213.
93. Stratos I, Li Z, Herlyn P, et al. (2013) Vitamin D increases cellular turnover and functionally restores the skeletal muscle after crush injury in rats. Am J Pathol 182, 895-904.
94. Matar M, Al-Shaar L, Maalouf J, et al. (2016) The relationship between calciotropic hormones, IGF-1, and bone mass across pubertal stages. J Clin Endocr Metab 101, 4860-4870.
95. Sollman AT, Al Khalaf F, AlHemaidi N, et al. (2008) Linear growth in relation to the circulating concentrations of insulinlike growth factor I, parathyroid hormone, and 25-hydroxy vitamin D in children with nutritional rickets before and after treatment: endocrine adaptation to vitamin D deficiency. Metabolism 57, 95-102.
96. Trummer C, Schwetz V, Pandis M, et al. (2017) Effects of vitamin D supplementation on IGF-1 and calcitriol: a randomized- controlled trial. Nutrients 9, E623.
97. Huhtakangas JA, Olivera CJ, Bishop JE, et al. (2004) The vitamin D receptor is present in caveolae-enriched plasma membranes and binds 1a,25(OH)2-vitamin D3 in vivo and in vitro. Mol Endocrinol 18, 2660-2671.
98. Buitrago CG, Arango NS & Boland RL (2012) 1a,25(OH)2D3- dependent modulation of Akt in proliferating and differentiating C2C12 skeletal muscle cells. J Cell Biochem 113, 1170-1181.
99. Morelli S, de Boland AR & Boland RL (1993) Generation of inositol phosphates, diacylglycerol and calcium fluxes in myoblasts treated with 1,25-dihydroxyvitamin D3. Biochem J 289, 675-679.
100. Capiati DA, Vazquez G, Tellez Inon MT, et al. (2000) Role of protein kinase C in 1,25(OH)2-vitamin D3 modulation of intracellular calcium during development of skeletal muscle cells in culture. J Cell Biochem 77, 200-212.
101. Vazquez G & de Boland AR (1996) Involvement of protein kinase C in the modulation of 1a,25-dihydroxy-vitamin D3-induced 45Ca2+ uptake in rat and chick cultured myoblasts. Biochim Biophys Acta 1310, 157-162.
102. 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.
103. Boland RL (2011) VDR activation of intracellular signaling pathways in skeletal muscle. Mol Cell Endocrinol 347,11-16.
104. Morelli S, Buitrago C, Boland R, et al. (2001) The stimulation of MAP kinase by 1,25(OH)2-vitamin D3 in skeletal muscle cells is mediated by protein kinase C and calcium. Mol Cell Endocrinol 173, 41-52.
105. Buitrago CG, Pardo VG, de Boland AR, et al. (2003) Activation of RAF-1 through Ras and protein kinase Ca mediates 1a,25(OH)2-vitamin D3 regulation of the mitogen-activated protein kinase pathway in muscle cells. J Biol Chem 278, 2199-2205.
106. Ronda AC, Buitrago C, Colicheo A, et al. (2007) Activation of MAPKs by 1a,25(OH)2-vitamin D3 and 17P-estradiol in skeletal muscle cells leads to phosphorylation of Elk-1 and CREB transcription factors. J Steroid Biochem Mol Biol 103, 462-466.
107. Buitrago CG, Ronda AC, de Boland AR, et al. (2006) MAP kinases p38 and JNK are activated by the steroid hormone 1a,25(OH)2-vitamin D3 in the C2C12 muscle cell line. J Cell Biochem 97, 698-708.
108. An SS, Fabry B, Mellema M, et al. (2004) Role of heat shock protein 27 in cytoskeletal remodeling of the airway smooth muscle cell. JAppl Physiol (1985) 96, 1701-1713.
109. Ordonez-Moran P & Munoz A (2009) Nuclear receptors: genomic and non-genomic effects converge. Cell Cycle 8, 1675-1680.
110. Yoshikawa S, Nakamura T, Tanabe H, et al. (1979) Osteomalacic myopathy. EndocrinolJpn 26, 65-72.
111. Ceglia L, Niramitmahapanya S, da Silva Morais M, et al. (2013) A randomized study on the effect of vitamin D3 supplementation on skeletal muscle morphology and vitamin D receptor concentration in older women. J Clin Endocrinol Metab 98, E1927-E1935.
112. Sorensen OH, Lund B, Saltin B, et al. (1979) Myopathy in bone loss of ageing: improvement by treatment with 1 a- hydroxycholecalciferol and calcium. Clin Sci (Lond) 56, 157-161.
113. Freedman LP (1999) Transcriptional targets of the vitamin D3 receptor-mediating cell cycle arrest and differentiation. JNutr 129, 581S-586S.
114. Sato Y, Iwamoto J, Kanoko T, et al. (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.
115. Wyon MA, Koutedakis Y, Wolman R, et al. (2014) The influence of winter vitamin D supplementation on muscle function and injury occurrence in elite ballet dancers: a controlled study./ Sci Med Sport 17, 8-12.
116. 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.
117. Stockton KA, Mengersen K, Paratz JD, et al. (2011) Effect of vitamin D supplementation on muscle strength: a systematic review and meta-analysis. Osteoporos Int 22, 859-871.
118. Beaudart C, Buckinx F, Rabenda V, et al. (2014) The effects of vitamin D on skeletal muscle strength, muscle mass, and muscle power: a systematic review and meta-analysis of randomized controlled trials. J Clin Endocrinol Metab 99, 4336-4345.
119. Houston DK, Tooze JA, Davis CC, et al. (2011) Serum 25-hydroxyvitamin D and physical function in older adults: the Cardiovascular Health Study All Stars. J Am Geriatr Soc 59, 1793-1801.
120. Menant JC, Close JCT, Delbaere K, et al. (2012) Relationships between serum vitamin D levels, neuromuscular and neuropsychological function and falls in older men and women. Osteoporosis Int 23, 981-989.
121. Scott D, Blizzard L, Fell J, et al. (2010) A prospective study of the associations between 25-hydroxyvitamin D, sarcopenia progression and physical activity in older adults. Clin Endocrinol 73, 581-587.
122. Michael YL, Smit E, Seguin R, et al. (2011) Serum 25- hydroxyvitamin D and physical performance in postmenopausal women. J Womens Health (Larchmt) 20, 1603-1608.
123. Houston DK, Tooze JA, Neiberg RH, et al. (2012) 25- Hydroxyvitamin D status and change in physical performance and strength in older adults: the Health, Aging, and Body Composition Study. Am J Epidemiol 176, 1025-1034.
124. Antoniak AE & Greig CA (2017) The effect of combined resistance exercise training and vitamin D3 supplementation on musculoskeletal health and function in older adults: a systematic review and meta-analysis. BMJ Open 7, e014619.
125. Chanet A, Verlaan S, Salles J, et al. (2017) Supplementing breakfast with a vitamin D and leucine-enriched whey protein medical nutrition drink enhances postprandial muscle protein synthesis and muscle mass in healthy older men. J Nutr 147, 2262-2271.
126. Wagatsuma A & Sakuma K (2014) Vitamin D signaling in myogenesis: potential for treatment of sarcopenia. Biomed Res Int 2014, 121254.
127. Sadat-Ali M, Al Elq AH, Al-Turki HA, et al. (2011) Influence of vitamin D levels on bone mineral density and osteoporosis. Ann Saudi Med 31, 602-608.
128. Neal S, Sykes J, Rigby M, et al. (2015) A review and clinical summary of vitamin D in regard to bone health and athletic performance. Phys Sportsmed 43, 161-168.
129. Lips P, Gielen E & van Schoor NM (2014) Vitamin D supplements with or without calcium to prevent fractures. Bonekey Rep 3, 512.
130. Ross AC, Manson JE, Abrams SA, et al. (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.
131. Zhao JG, Zeng XT, Wang J, et al. (2017) Association between calcium or vitamin D supplementation and fracture incidence in community-dwelling older adults: a systematic review and meta-analysis. JAMA 318, 2466-2482.
132. Barker T, Schneider ED, Dixon BM, etal. (2013) Supplemental vitamin D enhances the recovery in peak isometric force shortly after intense exercise. Nutr Metab (Lond) 10, 69.
133. Close GL, Leckey J, Patterson M, et al. (2013) The effects of vitamin D3 supplementation on serum total 25OHD concentration and physical performance: a randomised dose- response study. Br J Sports Med 47, 692-696.
134. Close GL, Russell J, Cobley JN, et al. (2013) Assessment of vitamin D concentration in non-supplemented professional athletes and healthy adults during the winter months in the UK: implications for skeletal muscle function. JSports Sci 31, 344-353.
135. Dubnov-Raz G, Livne N, Raz R, etal. (2015) Vitamin D supplementation and physical performance in adolescent swimmers. Int J Sport Nutr Exerc Metab 25, 317-325.
136. ToddJJ, McSorley EM, Pourshahidi LK, et al. (2017) Vitamin D3 supplementation using an oral spray solution resolves deficiency but has no effect on VO2 max in Gaelic footballers: results from a randomised, double-blind, placebo-controlled trial. Eur J Nutr 56, 1577-1587.
137. Fairbairn KA, Ceelen IJM, Skeaff CM, etal. (2018) Vitamin D3 supplementation does not improve sprint performance in professional rugby players: a randomized, placebo-controlled, double-blind intervention study. IntJ Sport Nutr Exerc Metab 28, 1-9.
138. Jastrzebska M, Kaczmarczyk M & Jastrzebski Z (2016) Effect of vitamin D supplementation on training adaptation in well- trained soccer players. J Strength Cond Res 30, 2648-2655.
139. Farrokhyar F, Sivakumar G, Savage K, et al. (2017) Effects of vitamin D supplementation on serum 25-hydroxyvitamin D concentrations and physical performance in athletes: a systematic review and meta-analysis of randomized controlled trials. Sports Medicine 47, 2323-2339.
140. Aloia JF & Li-Ng M (2007) Re: epidemic influenza and vitamin D. Epidemiol Infect 135, 1095-1096; author reply 1097-1098.
141. Giovannucci E (2009) Vitamin D and cardiovascular disease. Curr Atheroscler Rep 11, 456-461.
142. Lappe JM, Travers-Gustafson D, Davies KM, et al. (2007) Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr 85, 1586-1591.
143. Heaney RP, Dowell MS, Hale CA, et al. (2003) Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr 22, 142-146.
144. Trivedi DP, Doll R & Khaw KT (2003) Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ 326, 469.
145. Bischoff-Ferrari HA, Willett WC, Wong JB, et al. (2005) Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 293, 2257-2264.
146. Bischoff-Ferrari HA, Willett WC, Wong JB, et al. (2009) Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med 169, 551-561.
147. BiesalskiHK, Aggett PJ, Anton R, etal. (2011) 26th Hohenheim Consensus Conference, September 11, 2010 Scientific substantiation of health claims: evidence-based nutrition. Nutrition 27, S1-S20.
148. Heaney RP & Holick MF (2011) Why the IOM recommendations for vitamin D are deficient. J Bone Miner Res 26, 455-457.
149. Bischoff-Ferrari HA, Giovannucci E, Willett WC, et al. (2006) Estimation of optimal serum concentrations of 25- hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 84, 18-28.