Rapuri Prema B, Gallagher J C, Nawaz Zafar
Bone Metabolism Unit, Creighton University, School of Medicine, 601 North 30th Street, Omaha, NE 68131, USA.
J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):368-71. doi: 10.1016/j.jsbmb.2006.12.037. Epub 2007 Jan 12.
Of the various risk factors contributing to osteoporosis, dietary/lifestyle factors are important. In a clinical study we reported that women with caffeine intakes >300 mg/day had higher bone loss and women with vitamin D receptor (VDR) variant, tt were at a greater risk for this deleterious effect of caffeine. However, the mechanism of how caffeine effects bone metabolism is not clear. 1,25-Dihydroxy vitamin D(3) (1,25(OH)(2)D(3)) plays a critical role in regulating bone metabolism. The receptor for 1,25(OH)(2)D(3), VDR has been demonstrated in osteoblast cells and it belongs to the superfamily of nuclear hormone receptors. To understand the molecular mechanism of the role of caffeine in relation to bone, we tested the effect of caffeine on VDR expression and 1,25(OH)(2)D(3) mediated actions in bone. We therefore examined the effect of different doses of caffeine (0.2, 0.5, 1.0 and 10mM) on 1,25(OH)(2)D(3) induced VDR protein expression in human osteoblast cells. We also tested the effect of different doses of caffeine on 1,25(OH)(2)D(3) induced alkaline phosphatase (ALP) activity, a widely used marker of osteoblastic activity. Caffeine dose dependently decreased the 1,25(OH)(2)D(3) induced VDR expression and at concentrations of 1 and 10mM, VDR expression was decreased by about 50-70%, respectively. In addition, the 1,25(OH)(2)D(3) induced alkaline phosphatase activity was also reduced at similar doses thus affecting the osteoblastic function. The basal ALP activity was not affected with increasing doses of caffeine. Overall, our results suggest that caffeine affects 1,25(OH)(2)D(3) stimulated VDR protein expression and 1,25(OH)(2)D(3) mediated actions in human osteoblast cells.
在导致骨质疏松症的各种风险因素中，饮食/生活方式因素很重要。在一项临床研究中，我们报告称，咖啡因摄入量>300毫克/天的女性骨质流失更高，而携带维生素D受体（VDR）变体tt的女性因咖啡因的这种有害作用面临更大风险。然而，咖啡因影响骨代谢的机制尚不清楚。1,25-二羟基维生素D（3）（1,25（OH）2D（3））在调节骨代谢中起关键作用。1,25（OH）2D（3）的受体VDR已在成骨细胞中得到证实，它属于核激素受体超家族。为了解咖啡因在骨骼方面作用的分子机制，我们测试了咖啡因对VDR表达以及1,25（OH）2D（3）介导的骨骼作用的影响。因此，我们研究了不同剂量的咖啡因（0.2、0.5、1.0和10毫摩尔）对1,25（OH）2D（3）诱导人成骨细胞中VDR蛋白表达的影响。我们还测试了不同剂量的咖啡因对1,25（OH）2D（3）诱导的碱性磷酸酶（ALP）活性的影响，ALP活性是成骨细胞活性广泛使用的标志物。咖啡因剂量依赖性地降低了1,25（OH）2D（3）诱导的VDR表达，在1和10毫摩尔浓度下，VDR表达分别降低了约50-70%。此外，在相似剂量下，1,25（OH）2D（3）诱导的碱性磷酸酶活性也降低，从而影响成骨细胞功能。随着咖啡因剂量增加，基础ALP活性不受影响。总体而言，我们的数据表明咖啡因会影响1,25（OH）2D（3）刺激的VDR蛋白表达以及1,25（OH）2D（3）介导的人成骨细胞作用。
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