Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-1241, Japan.
Arch Biochem Biophys. 2012 Jul 1;523(1):22-9. doi: 10.1016/j.abb.2011.11.011. Epub 2011 Nov 15.
Vitamin D was discovered as an anti-rachitic agent, but even at present, there is no direct evidence to support the concept that vitamin D directly stimulates osteoblastic bone formation and mineralization. It appears to be paradoxical, but vitamin D functions in the process of osteoclastic bone resorption. In 1952, Carlsson reported that administration of vitamin D(3) to rats fed a vitamin D-deficient, low calcium diet raised serum calcium levels. Since the diet did not contain appreciable amounts of calcium, the rise in serum calcium was considered to be derived from bone. Since then, this assay has been used as a standard bioassay for vitamin D compounds. Osteoclasts, the cells responsible for bone resorption, develop from hematopoietic cells of the monocyte-macrophage lineage. Several lines of evidence have shown that the active form of vitamin D(3), 1α,25-dihydroxyvitamin D(3) [1α,25(OH)(2)D(3)] is one of the most potent inducers of receptor activator of NF-κB ligand (RANKL), a key molecule for osteoclastogenesis, in vitro. In fact, 1α,25(OH)(2)D(3) strongly induced osteoclast formation and bone resorption in vitro. Nevertheless, 1α,25(OH)(2)D(3) and its prodrug, Alfacalcidol (1α-hydroxyvitamin D(3)) have been used as therapeutic agents for osteoporosis since 1983, because they increase bone mineral density and reduce the incidence of bone fracture in vivo. Furthermore, a new vitamin D analog, Eldecalcitol [2β-(3-hydroxypropoxy)-1α,25(OH)(2)D(3)], has been approved as a new drug for osteoporosis in Japan in January 2011. Interestingly, these beneficial effects of in vivo administration of vitamin D compounds are caused by the suppression of osteoclastic bone resorption. The present review article describes the mechanism of the discrepancy of vitamin D compounds in osteoclastic bone resorption between in vivo and in vitro.
维生素 D 最初被发现是一种抗佝偻病因子，但即使在现在，也没有直接的证据支持维生素 D 直接刺激成骨细胞骨形成和矿化的概念。这似乎很矛盾，但维生素 D 在破骨细胞骨吸收的过程中发挥作用。1952 年，Carlsson 报道称，给喂食维生素 D 缺乏、低钙饮食的大鼠施用维生素 D(3)会提高血清钙水平。由于饮食中不含有可观数量的钙，因此血清钙的升高被认为来自于骨骼。从那时起，这种测定方法一直被用作维生素 D 化合物的标准生物测定法。破骨细胞是负责骨吸收的细胞，它们起源于单核细胞-巨噬细胞谱系的造血细胞。有几条证据表明，维生素 D(3)的活性形式，1α,25-二羟维生素 D(3)[1α,25(OH)(2)D(3)]，是体外破骨细胞生成的关键分子核因子-κB 受体激活剂配体（RANKL）的最有效诱导剂之一。事实上，1α,25(OH)(2)D(3)在体外强烈诱导破骨细胞形成和骨吸收。然而，1α,25(OH)(2)D(3)及其前药，阿法骨化醇（1α-羟维生素 D(3))自 1983 年以来一直被用作骨质疏松症的治疗药物，因为它们增加了骨矿物质密度并降低了体内骨折的发生率。此外，一种新的维生素 D 类似物，艾地骨化醇[2β-(3-羟丙氧基)-1α,25(OH)(2)D(3)]，已于 2011 年 1 月在日本被批准为骨质疏松症的新药。有趣的是，这些维生素 D 化合物在体内给药的有益效果是通过抑制破骨细胞骨吸收来实现的。本文综述了维生素 D 化合物在体内和体外破骨细胞骨吸收中的差异机制。
