Goltzman David, Miao Dengshun, Panda Dibyendu K, Hendy Geoffrey N
Calcium Research Laboratory, McGill University Health Centre, 687 Pine Avenue West, Room H4.67, Montreal, Que., Canada H3A 1A1.
J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):485-9. doi: 10.1016/j.jsbmb.2004.03.058.
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.
对编码1,25 - 二羟基维生素D[1,25(OH)₂D]合成酶（25 - 羟基维生素D - 1α - 羟化酶[1α(OH)ase或CYP27B1]）以及1,25(OH)₂D核受体（维生素D受体，VDR）的基因进行靶向缺失，已为遗传性人类疾病维生素D依赖性佝偻病I型和II型提供了有用的小鼠模型。我们利用这些模型和双基因敲除突变体来研究钙以及1,25(OH)₂D/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)₂D和VDR两者。骨骼矿化依赖于充足的环境钙，但并不直接需要1,25(OH)₂D/VDR系统。甲状旁腺激素（PTH）分泌也主要受环境血清钙的调节，但突变体所表现出的甲状旁腺增大以及软骨生长板增宽，只有通过钙和1,25(OH)₂D的联合作用才能恢复正常，这显然与VDR无关。最佳的破骨细胞骨吸收和成骨细胞骨形成都需要完整的1,25(OH)₂D/VDR机制。结果表明，在骨骼和矿物质稳态中，钙不能完全替代维生素D，但这两种物质具有离散且重叠的功能。
