Effects of calcium and of the Vitamin D system on skeletal and calcium homeostasis: lessons from genetic models
Effects of calcium and of the Vitamin D system on skeletal and calcium homeostasis: lessons from genetic models
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DOI：
10.1016/j.jsbmb.2004.03.058
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发表时间：
2004-05-01
影响因子：
4.1
通讯作者：
Hendy, GN
中科院分区：
文献类型：
--
作者：
Goltzman, D;Miao, DS;Hendy, GN
编码1，25-二羟基维生素D [1，25（OH）（2）D]-合成酶、25羟基维生素D-1 α-羟化酶[1 α（OH）ase或CYP 27 B1]和1，25（OH）（2）D核受体、维生素D受体（VDR）的基因的靶向缺失提供了有用的遗传性人类疾病维生素D依赖性佝偻病I型和II型的小鼠模型。我们采用这些模型和双无效突变体来研究钙和1，25（OH）（2）D/VDR系统对骨骼和钙稳态的影响。最佳的膳食钙吸收需要1，25（OH）（2）D和VDR。骨骼肌矿化依赖于充足的环境钙，但不直接需要1，25（OH）（2）D/VDR系统。甲状旁腺激素（PTH）分泌也主要受周围血清钙的调节，但突变体表现出的增大的甲状旁腺和加宽的软骨生长板只能通过钙和1，25（OH）（2）D的组合来正常化，显然与VDR无关。最佳的成骨细胞骨吸收和成骨细胞骨形成都需要完整的1，25（OH）（2）D/VDR装置。结果表明，钙不能完全取代维生素D在骨骼和矿物质的稳态，但这两个代理商有离散和重叠的功能。(C)2004爱思唯尔有限公司保留所有权利。
Targeted deletion of genes encoding the 1,25-dihydroxyVitamin D [1,25 (OH)(2)D]-synthesizing enzyme, 25 hydroxyVitamin D-1alpha-hydroxylase [1alpha(OH)ase or CYP27B1], and of the nuclear receptor for 1,25(OH)(2)D, the Vitamin D receptor (VDR), have provided useful mouse models of the inherited human diseases, Vitamin D-dependent rickets types I and II. We employed these models and double null mutants to examine the effects of calcium and of the 1,25(OH)(2)D/VDR system on skeletal and calcium homeostasis. Optimal dietary calcium absorption required both 1,25(OH)(2)D and the VDR. Skeletal mineralization was dependent on adequate ambient calcium but did not directly require the 1,25(OH)(2)D/VDR system. Parathyroid hormone (PTH) secretion was also modulated primarily by ambient serum calcium but the enlarged parathyroid glands which the mutants exhibited and the widened cartilaginous growth plates could only be normalized by the combination of calcium and 1,25(OH)(2)D, apparently independently of the VDR. Optimal osteoclastic bone resorption and osteoblastic bone formation both required an intact 1,25(OH)(2)D/VDR apparatus. The results indicate that calcium cannot entirely substitute for Vitamin D in skeletal and mineral homeostasis but that the two agents have discrete and overlapping functions. (C) 2004 Elsevier Ltd. All rights reserved.