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 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.