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.

1,25(OH)2D3regulates the proangiogenic activity of pericyte through VDR‐mediated modulation of VEGF production and signaling of VEGF and PDGF receptors

“…The majority of vitamin D action is mediated through its receptor, and 1,25(OH) 2 D 3 increases VDR expression in various cell types . To further explain the observed inhibitory effect of 1,25(OH) 2 D 3 on PC, we examined VDR expression in PC.…”

A reverse genetics cell‐based evaluation of genes linked to healthy human tissue age

“…Human primary skeletal muscle cells were established from muscle biopsy samples from healthy young adult men as previously described (12). This procedure was approved by the ethics committee of the Karolinska Institutet (Stockholm, Sweden).…”

Non-classical effects of vitamin D

“…Предпо-лагается, что VDR экспрессируется в очень низких ко-личествах в покоящихся мышцах, а активация экспрес-сии происходит в определенных условиях, например, при стрессе. Исследование на моделях, использующих животных различного возраста, предполагает измене-ние экспрессии с возрастом и различную роль VDR в раз-вивающейся и зрелой мышечной ткани [81]; при воз-действии витамина D показано повышение экспрессии VDR в мышечной ткани человека [82], а также быстрые, нетранскрипционные эффекты в мышиной скелетной мускулатуре [83]. Предстоит определить, вызваны ли эффекты витамина D напрямую активацией VDR или опо-средованы изменениями абсорбции кальция, влияющи-ми на секрецию ПТГ и на внутриклеточные уровни каль-ция [61].…”