Effects of 1,25-Dihydroxyvitamin D^sub 3^ and Vitamin D^sub 3^ on the Expression of the Vitamin D Receptor in Human Skeletal Muscle Cells

• Published in: Calcified tissue international Vol. 96; no. 3; p. 256
• Main Authors: Pojednic, Rachele M, Ceglia, Lisa, Olsson, Karl, Gustafsson, Thomas, Lichtenstein, Alice H, Dawson-hughes, Bess, Fielding, Roger A
• Format: Journal Article
• Language: English
• Published: New York Springer Nature B.V 01.03.2015
• Subjects: Gene expression; Musculoskeletal system; Vitamin D
• ISSN: 0171-967X; 1432-0827
• DOI: 10.1007/s00223-014-9932-x

Issue Title: Special Issue: Skeletal Muscle in Health and Disease 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^sub 3^ (1,25(OH)^sub 2^D^sub 3^) on VDR gene expression in human primary myoblasts, (2) effect of 16-week supplementation with vitamin D^sub 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)^sub 2^D^sub 3^ for 18 h. A dose-dependent treatment effect was noted with 1 nmol/L of 1,25OH2D^sub 3^ 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 D^sub 3^ supplementation (4,000 IU/day) in older adults. Intramuscular VDR mRNA was significantly different from placebo after 16 weeks of vitamin D^sub 3^ (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 1,25OH2D^sub 3^ in human myoblasts. 25OHD is associated with VDR protein and 16 weeks of supplementation with vitamin D^sub 3^ resulted in a persistent increase in VDR gene expression of vitamin D^sub 3^ in muscle tissue biopsies. These findings suggest treatment with vitamin D compounds results in sustained increases in VDR in human skeletal muscle.