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Title: Effects of 1,25-dihydroxyvitamin D3 and vitamin D3 on the expression of the vitamin D receptor in human skeletal muscle cells

Author
item POJEDNIC, RACHELE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item CEGLIA, LISA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item OLSSON, KARL - Karolinska Institute
item GUSTAFSSON, THOMAS - Karolinska Institute
item LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item FIELDING, ROGER - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Calcified Tissue International
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/15/2014
Publication Date: 12/6/2014
Citation: Pojednic, R., Ceglia, L., Olsson, K., Gustafsson, T., Lichtenstein, A.H., Dawson-Hughes, B., Fielding, R.A. 2014. Effects of 1,25-dihydroxyvitamin D3 and vitamin D3 on the expression of the vitamin D receptor in human skeletal muscle cells. Calcified Tissue International. 96(3):256-263.

Interpretive Summary: The vitamin D receptor (VDR) is expressed in many tissues in the body. Data on the activity and expression of VDR in human skeletal muscle is lacking. We conducted a series of studies to examine: 1) the effect of circulating active vitamin D on VDR gene expression in human muscle cells, 2) the effect of 16 weeks of vitamin D supplementation on muscle VDR gene expression in older women and 3) the association between serum vitamin D and VDR protein concentration in older men and women. A dose-dependent increase in muscle cell VDR was seen with increasing doses of active vitamin D in human muscle cells. Muscle VDR gene expression was also increased after 16 weeks of vitamin D supplementation in older women. Lastly, serum vitamin D was associated with muscle cell VDR protein in older men and women. These findings suggest treatment with vitamin D may result in sustained increases in VDR in human skeletal muscle cells.

Technical Abstract: 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.