The Effect of Caffeine on Calcitriol-Inducible Vitamin D Receptor-Controlled Gene Expression in Intestinal and Osteoblastic Cells
CALCIFIED TISSUE INTERNATIONAL
Authors: Zenata, Ondrej; Marcalikova, Adele; Vrzal, Radim
Abstract
Some epidemiological studies suggested caffeine consumption as the cause for bone mineral density loss. Certain genes involved in this process are regulated by vitamin D receptor (VDR). Therefore, we investigated if caffeine can affect inducible expression of VDR-regulated genes, some of them being involved in bone mineralization process. By employing reporter gene assay, polymerase chain reaction, and western blotting, we monitored the VDR activity and expression in cell cultures of intestinal (LS180), osteosarcoma (HOS), and normal human osteoblasts in vitro. While caffeine stimulated calcitriol-inducible VDR-dependent nanoluciferase activity in stable reporter cell line IZ-VDRE (derived from LS180), it rather modulated mRNA levels of target genes, like CYP24A1, BGLAP, SPP1, and TNSF11 in LS180 and HOS cells. However, caffeine significantly decreased calcitriol-inducible CYP24A1, TNSF11, and SPP1 transcripts in osteoblasts. This decrease had non-linear U-shaped profile. Our in vitro data demonstrate biphasic action of caffeine on the expression of certain calcitriol-inducible VDR-regulated genes in normal human osteoblasts.
Epigenetics Predicts Serum 25-Hydroxyvitamin D Response to Vitamin D-3 Supplementation in African Americans
MOLECULAR NUTRITION & FOOD RESEARCH
Authors: Chen, Li; Dong, Yanbin; Chen, Jie; Huang, Ying; Zhu, Haidong
Abstract
Scope The effects of vitamin D-3 supplementations on circulating 25-hydroxyvitamin D [25(OH)D] are varied. The hypothesis that the baseline DNA methylation plays a role in the serum 25(OH)D response to vitamin D-3 supplementation is tested. Methods and results A randomized clinical trial is first conducted among 64 African Americans, who are randomly assigned to a placebo or a 16-week treatment of 600, 2000, and 4000 IU d(-1) of vitamin D-3 supplements. Expected serum 25(OH)D concentrations at posttest are estimated by intervention, age, gender, body mass index, baseline 25(OH)D concentrations, and seasonal variations. The 25(OH)D response is categorized into a high-response group when the actual 25(OH)D concentrations at posttest are higher than expected, and a low-response group otherwise. The 25(OH)D response is associated with baseline methylation levels of CYP family and VDR genes (raw p < 0.05). At a genome-wide level, the baseline methylation level of cg07873128 (OSBPL5) that regulates cholesterol balance and calcium homeostasis is higher in the low-response group (false discovery rate = 0.028). Conclusions The baseline methylation levels of CYP family and VDR modulate 25(OH)D response. In addition, the hypermethylation of cg07873128 at the baseline, which is located in the imprinted gene OSBPL5, may reduce the serum 25(OH)D response to vitamin D-3 supplementation.