title: Effects of 1,25-dihydroxyvitamin D3 and vitamin D3 on the expression of the vitamin d receptor in human skeletal muscle cells.
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.
authors.affiliation: Nutrition, Exercise Physiology and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington St., Boston, MA, 02111, USA, rachele.pojednic@joslin.harvard.edu.
authors.forename: Rachele M
authors.initials: RM
authors.lastname: Pojednic
authors.forename: Lisa
authors.initials: L
authors.lastname: Ceglia
authors.forename: Karl
authors.initials: K
authors.lastname: Olsson
authors.forename: Thomas
authors.initials: T
authors.lastname: Gustafsson
authors.forename: Alice H
authors.initials: AH
authors.lastname: Lichtenstein
authors.forename: Bess
authors.initials: B
authors.lastname: Dawson-Hughes
authors.forename: Roger A
authors.initials: RA
authors.lastname: Fielding
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology*; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D018167:Receptors, Calcitriol / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D018167:Receptors, Calcitriol; D002762:Cholecalciferol; D002117:Calcitriol