Effects of 1,25-Dihydroxyvitamin D3 and Vitamin D3 on the Expression of the Vitamin D Receptor in Human Skeletal Muscle Cells
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Vitamin D receptor (VDR) expression and action in non-human skeletal muscle have recently been reported in several studies, yet data on the activity and expression of VDR in human muscle cells are scarce. We conducted a series of studies to examine the (1) effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on VDR gene expression in human primary myoblasts, (2) effect of 16-week supplementation with vitamin D3 on intramuscular VDR gene expression in older women, and (3) association between serum 25-hydroxyvitamin D (25OHD) and intramuscular VDR protein concentration in older adults. Human primary myoblasts were treated with increasing concentrations of 1,25(OH)2D3 for 18 h. A dose-dependent treatment effect was noted with 1 nmol/L of 1,25OH2D3 increasing intramuscular VDR mRNA expression (mean fold change ± SD 1.36 ± 0.33; P = 0.05). Muscle biopsies were obtained at baseline and 16 weeks after vitamin D3 supplementation (4,000 IU/day) in older adults. Intramuscular VDR mRNA was significantly different from placebo after 16 weeks of vitamin D3 (1.2 ± 0.99; −3.2 ± 1.7, respectively; P = 0.04). Serum 25OHD and intramuscular VDR protein expression were examined by immunoblot. 25OHD was associated with intramuscular VDR protein concentration (R = 0.67; P = 0.0028). In summary, our study found VDR gene expression increases following treatment with 1,25OH2D3 in human myoblasts. 25OHD is associated with VDR protein and 16 weeks of supplementation with vitamin D3 resulted in a persistent increase in VDR gene expression of vitamin D3 in muscle tissue biopsies. These findings suggest treatment with vitamin D compounds results in sustained increases in VDR in human skeletal muscle.
KeywordsVitamin D Skeletal muscle Vitamin D receptor Human Primary myoblasts Aging
USDA Agricultural Research Service, under Agreement Nos. 58-1950-7-707 (to BDH and LC) and 58-1950-0-014 (to RAF); The Dairy Research Institute (R.A.F.), Boston Claude D. Pepper Older Americans Independence Center (1P30AG031679 to R.A.F.), the Boston Nutrition/Obesity Research Center (DK046200 to R.A.F.), and an NHLBI pre-doctoral training grant (T32HL69772 to RMP). Any opinions, findings, conclusion, or recommendation expressed in this publication are those of the author(s) and do not necessarily reflect the views of the U.S. Department of Agriculture.
Conflict of Interest
Rachele Pojednic, Lisa Ceglia, Karl Olsson, Thomas Gustafsson, Alice Lichtenstein, Bess Dawson-Hughes, and Roger Fielding declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5).
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