Effects of 1,25-Dihydroxyvitamin D3 and Vitamin D3 on the Expression of the Vitamin D Receptor in Human Skeletal Muscle Cells

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 D-3 (1,25(OH)(2)D-3) on VDR gene expression in human primary myoblasts, (2) effect of 16-week supplementation with vitamin D-3 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)(2)D-3 for 18 h. A dose-dependent treatment effect was noted with 1 nmol/L of 1,25OH(2)D(3) increasing intramuscular VDR mRNA expression (mean fold change +/- A SD 1.36 +/- A 0.33; P = 0.05). Muscle biopsies were obtained at baseline and 16 weeks after vitamin D-3 supplementation (4,000 IU/day) in older adults. Intramuscular VDR mRNA was significantly different from placebo after 16 weeks of vitamin D-3 (1.2 +/- A 0.99; -3.2 +/- A 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 1,25OH(2)D(3) in human myoblasts. 25OHD is associated with VDR protein and 16 weeks of supplementation with vitamin D-3 resulted in a persistent increase in VDR gene expression of vitamin D-3 in muscle tissue biopsies. These findings suggest treatment with vitamin D compounds results in sustained increases in VDR in human skeletal muscle.