Vitamin D: calcium and bone homeostasis during evolution.
Vitamin D: calcium and bone homeostasis during evolution.
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DOI：
10.1038/bonekey.2013.214
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发表时间：
2014-01-08
期刊：
影响因子：
--
通讯作者：
Suda, Tatsuo
中科院分区：
文献类型：
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作者：
Bouillon, Roger;Suda, Tatsuo
维生素D3在生命进化的早期就已经被发现，但本质上是7-脱氢胆固醇与紫外光b光化学反应的非活性最终产物。一个完整的维生素D（指维生素D2和D3）内分泌系统，其特征是特定的VDR（维生素D受体，核受体家族成员），特定的维生素D代谢CYP450酶由嗜钙激素调节和专用的血浆转运蛋白只在脊椎动物中发现。在最早的脊椎动物（七鳃鳗）中，维生素D代谢和VDR很可能起源于共同的PRX/VDR祖先基因的复制，作为外源解毒途径的一部分。然而，维生素D内分泌系统随后成为广泛钙化骨骼钙供应的重要调节器。维生素D对于维持正常的钙和骨骼平衡至关重要，这一点在缺乏维生素D的生长中的两栖动物、爬行动物、鸟类和哺乳动物的佝偻病中得到了证明。从两栖动物开始，骨逐渐变得更加动态，骨吸收受到调节，主要是通过PTH和1 α，25-二羟基维生素D3 （1,25(OH)2D3）共同作用于多核破骨细胞的产生和功能。因此，在破骨细胞的控制下，骨的功能是一个巨大的内部钙库。骨细胞还表现出一系列显著的活动，包括机械传感和调节矿物质稳态，但也在全球营养和能量稳态中发挥重要作用。从爬行动物开始，矿化是由调控良好的兄弟蛋白和相关酶控制的，几乎都是由125 (OH)2D3控制的。因此，维生素D的故事从惰性分子开始，但在陆生动物钙和骨骼平衡中发挥了重要作用，以应对更高重力和缺钙环境的挑战。
Vitamin D3 is already found early in the evolution of life but essentially as inactive end products of the photochemical reaction of 7-dehydrocholestol with ultraviolet light B. A full vitamin D (refers to vitamin D2 and D3) endocrine system, characterized by a specific VDR (vitamin D receptor, member of the nuclear receptor family), specific vitamin D metabolizing CYP450 enzymes regulated by calciotropic hormones and a dedicated plasma transport-protein is only found in vertebrates. In the earliest vertebrates (lamprey), vitamin D metabolism and VDR may well have originated from a duplication of a common PRX/VDR ancestor gene as part of a xenobiotic detoxification pathway. The vitamin D endocrine system, however, subsequently became an important regulator of calcium supply for an extensive calcified skeleton. Vitamin D is essential for normal calcium and bone homeostasis as shown by rickets in vitamin D-deficient growing amphibians, reptiles, birds and mammals. From amphibians onward, bone is gradually more dynamic with regulated bone resorption, mainly by combined action of PTH and 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the generation and function of multinucleated osteoclasts. Therefore, bone functions as a large internal calcium reservoir, under the control of osteoclasts. Osteocytes also display a remarkable spectrum of activities, including mechanical sensing and regulating mineral homeostasis, but also have an important role in global nutritional and energy homeostasis. Mineralization from reptiles onward is under the control of well-regulated SIBLING proteins and associated enzymes, nearly all under the control of 1,25(OH)2D3. The vitamin D story thus started as inert molecule but gained an essential role for calcium and bone homeostasis in terrestrial animals to cope with the challenge of higher gravity and calcium-poor environment.