Nongenomic effects of 1α,25-dihydroxyvitamin D3 on cartilage formation deduced from comparisons between Cyp27b1 and Vdr knockout mice
Nongenomic effects of 1α,25-dihydroxyvitamin D3 on cartilage formation deduced from comparisons between Cyp27b1 and Vdr knockout mice
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DOI：
10.1016/j.bbrc.2016.12.139
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发表时间：
2017-01-29
影响因子：
3.1
通讯作者：
Okano, Toshio
中科院分区：
文献类型：
--
作者：
Hirota, Yoshihisa;Nakagawa, Kimie;Okano, Toshio
维生素D的活性形式，1 α，25-二羟基维生素D3（1 α，25 D3），通过核维生素D受体（VDR）在维持钙（Ca）稳态、骨形成和细胞增殖和分化中起重要作用。通过肾脏中的25羟基维生素D 1 α-羟化酶（CYP 27 B1）在1 α位对维生素D进行羟基化而形成。然而，Cyp 27 B1（-/-）小鼠，缺乏CYP 27 B1，和VDR-缺陷小鼠（Vdr（-/-））尚未得到广泛的研究，特别是在比较框架。为了阐明1 α、25 D3和VDR的生理学意义，我们产生Cyp 27 b1（-/-）小鼠，并将它们的表型与VDR（-/-）小鼠的表型进行比较。Cyp 27 b1（-/-）小鼠表现出低钙血症、生长缺陷和骨骼发生功能障碍，与Vdr（-/-）小鼠相似。然而，与Cyp 27 b1（-/-）小鼠不同，Vdr（-/-）小鼠发生脱发。Cyp 27 b1（-/-）小鼠表现出软骨块形成，后肢行走困难。此外，对Cyp 27 b1（-/-）小鼠进行表型分析，提供高Ca饮食以校正Ca代谢异常。此外，还研究了不受Ca代谢调节活性介导的1 α，25 D3的作用。即使纠正了血Ca浓度，Cyp 27 b1（-/-）小鼠的生长和软骨组织形成异常也没有改善。这些结果表明，1 α，25 D3直接控制软骨细胞的增殖和分化。使用Cyp 27 b1（-/-）在这项研究中产生的小鼠，我们可以分析的生理作用的新型维生素D衍生物在缺乏内源性1 α，25 D3。因此，本研究为开发有效治疗和预防骨质疏松症的新型维生素D制剂提供了有用的动物模型。(C)2016作者爱思唯尔公司出版这是一个在CC BY-NC-ND许可证下的开放获取文章（http：//creativecommons.org/licenses/by-nc-nd/4.0/）。
The active form of vitamin D, 1 alpha, 25-dihydroxyvitamin D3 (1 alpha, 25D3), plays an important role in the maintenance of calcium (Ca) homeostasis, bone formation, and cell proliferation and differentiation via nuclear vitamin D receptor (VDR). It is formed by the hydroxylation of vitamin D at the 1 alpha position by 25hydroxyvitamin D 1 alpha-hydroxylase (CYP27B1) in the kidney. However, Cyp27b1(-/-) mice, deficient in CYP27B1, and VDR-deficient mice (Vdr(-/-)) have not been extensively examined, particularly in a comparative framework. To clarify the physiological significance of 1 alpha, 25D3 and VDR, we produced Cyp27b1(-/-) mice and compared their phenotypes with those of Vdr(-/-) mice. Cyp27b1(-/-) mice exhibited hypocalcemia, growth defects, and skeletogenesis dysfunction, similar to Vdr(-/-) mice. However, unlike Cyp27b1(-/-) mice, Vdr(-/-) mice developed alopecia. Cyp27b1(-/-) mice exhibited cartilage mass formation and had difficulty walking on hindlimbs. Furthermore, a phenotypic analysis was performed on Cyp27b1(-/-) mice provided a high Ca diet to correct for the Ca metabolic abnormality. In addition, the effects of 1 alpha, 25D3 that are not mediated by Ca metabolic regulatory activity were investigated. Even when the blood Ca concentration was corrected, abnormalities in growth and cartilage tissue formation did not improve in Cyp27b1(-/-) mice. These results suggested that 1 alpha, 25D3 directly controls chondrocyte proliferation and differentiation. Using Cyp27b1(-/-) mice produced in this study, we can analyze the physiological effects of novel vitamin D derivatives in the absence of endogenous 1 alpha, 25D3. Accordingly, this study provides a useful animal model for the development of novel vitamin D formulations that are effective for the treatment and prevention of osteoporosis. (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).