Mechanisms involved in bone resorption regulated by vitamin D
Mechanisms involved in bone resorption regulated by vitamin D
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DOI：
10.1016/j.jsbmb.2017.11.005
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发表时间：
2018-03-01
影响因子：
4.1
通讯作者：
Takahashi, Naoyuki
中科院分区：
文献类型：
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作者：
Nakamichi, Yuko;Udagawa, Nobuyuki;Takahashi, Naoyuki
维生素D的活性形式通过成骨细胞谱系细胞（由成骨细胞和骨细胞组成）中的维生素D受体（VDR）在体外和体内增强破骨细胞生成。这种促吸收活性基本上是明显的，活性维生素D的浓度高于生理条件下的预期浓度。然而，在日本，维生素D化合物已用于治疗骨质疏松症以增加骨矿物质密度（BMD）。值得注意的是，通过长期使用药理学（=接近生理学）剂量的维生素D化合物治疗，BMD的增加是由骨吸收的抑制引起的。因此，维生素D是否表达促吸收或抗吸收特性似乎取决于治疗方案。我们分别使用Osterix-Cre转基因小鼠和Cathepsin K-Cre敲入小鼠建立了成骨细胞谱系特异性和破骨细胞特异性VDR条件性敲除（cKO）小鼠。根据我们使用这些cKO小鼠系的观察，无论是成骨细胞系细胞还是破骨细胞中的VDR，都对破骨细胞生成和稳态时的骨吸收起重要作用。然而，使用我们的cKO系，我们观察到成骨细胞系细胞中的VDR，而不是破骨细胞，参与体内药理剂量的维生素D化合物的抗吸收特性。报告了两种不同的成骨细胞系VDR cKO小鼠系。一种是使用α 1，I型胶原（Colla 1）-Cre转基因小鼠的VDR cKO小鼠系（在此我们称为Collal-VDR-cKO小鼠），另一种是使用牙本质基质蛋白1（Dmpl）-Cre转基因小鼠的VDR cKO小鼠系（Dmpl-VDR-cKO小鼠）。由于骨吸收降低，Collal-VDR-cKO小鼠的骨量略有增加。相比之下，Dmpl-VDR-cKO小鼠在BMD方面没有表现出差异，这与我们关于ObVDR-cKO小鼠的结果一致。在这里，我们详细讨论了维生素D在骨吸收中的相互矛盾的结果和多种作用模式。(279字）
Active forms of vitamin D enhance osteoclastogenesis in vitro and in vivo through the vitamin D receptor (VDR) in osteoblast-lineage cells consisting of osteoblasts and osteocytes. This pro-resorptive activity was evident basically with higher concentrations of active vitamin D than those expected in physiological conditions. Nevertheless, vitamin D compounds have been used in Japan for treating osteoporosis to increase bone mineral density (BMD). Of note, the increase in BMD by long-term treatment with pharmacological ( = near-physiological) doses of vitamin D compounds was caused by the suppression of bone resorption. Therefore, whether vitamin D expresses pro-resorptive or anti-resorptive properties seems to be dependent on the treatment protocols. We established osteoblast lineage-specific and osteoclast-specific VDR conditional knockout (cKO) mice using Osterix-Cre transgenic mice and Cathepsin K-Cre knock-in mice, respectively. According to our observation using these cKO mouse lines, neither VDR in osteoblast-lineage cells nor that in osteoclasts played important roles for osteoclastogenesis and bone resorption at homeostasis. However, using our cKO lines, we observed that VDR in osteoblast-lineage cells, but not osteoclasts, was involved in the anti-resorptive properties of pharmacological doses of vitamin D compounds in vivo. Two different osteoblast-lineage VDR cKO mouse lines were reported. One is a VDR cKO mouse line using alpha 1, type I collagen (Colla 1)-Cre transgenic mice (here we call Collal-VDR-cKO mice) and the other is that using dentin matrix protein 1 (Dmpl)-Cre transgenic mice (Dmpl-VDR-cKO mice). Collal-VDR-cKO mice exhibited slightly increased bone mass due to lowered bone resorption. In contrast, Dmpl-VDR-cKO mice exhibited no difference in BMD in agreement with our results regarding ObVDR-cKO mice. Here we discuss contradictory results and multiple modes of actions of vitamin D in bone resorption in detail. (279 words)