Evaluation of keratinocyte proliferation and differentiation in vitamin D receptor knockout mice.
Evaluation of keratinocyte proliferation and differentiation in vitamin D receptor knockout mice.
复制标题
DOI：
10.1210/endo.141.6.7515
复制
发表时间：
2000-06
期刊：
影响因子：
4.8
通讯作者：
Yoshiyuki Sakai;M. Demay
中科院分区：
文献类型：
--
作者：
Yoshiyuki Sakai;M. Demay
1,25-二羟基维生素 D3 的生物效应是由核受体维生素 D 受体 (VDR) 介导的。小鼠体内 VDR 的靶向消融会导致低钙血症、低磷血症、甲状旁腺功能亢进、佝偻病、骨软化症和脱发。矿物质离子稳态的正常化可以防止这些异常（脱发除外）。由于 1,25(OH)2D3 已被证明在角质形成细胞增殖和分化中发挥作用，因此我们对从 VDR 无效小鼠分离的原代角质形成细胞和皮肤进行了研究，以确定角质形成细胞异常是否可以解释所观察到的脱发。 VDR无效和野生型角质形成细胞的基础增殖率在增殖和分化条件下是相同的。 4 日龄时体内角质形成细胞增殖的评估证实 VDR 消融没有显着效果。与从对照同窝小鼠分离的角质形成细胞相比，从 VDR 消融小鼠分离的角质形成细胞中，角质形成细胞分化标志物（角蛋白 1、外皮蛋白和兜甲蛋白）的基础表达没有差异。同样，这些基因的体内表达在 4 日龄时也没有改变。当 18 天龄时通过脱毛诱导生长期时，VDR 缺失小鼠在毛发周期的启动方面受到严重损害。这些数据表明，VDR 无效小鼠的脱发并非归因于角质形成细胞增殖或分化的内在缺陷，而是归因于毛发周期起始的异常。
The biological effects of 1,25-dihydroxyvitamin D3 are mediated by a nuclear receptor, the vitamin D receptor (VDR). Targeted ablation of the VDR in mice results in hypocalcemia, hypophosphatemia, hyperparathyroidism, rickets, osteomalacia, and alopecia. Normalization of mineral ion homeostasis prevents these abnormalities with the exception of the alopecia. Because 1,25(OH)2D3 has been shown to play a role in keratinocyte proliferation and differentiation, we undertook studies in primary keratinocytes and skin isolated from VDR null mice to determine if a keratinocyte abnormality could explain the alopecia observed. The basal proliferation rate of the VDR null and wild-type keratinocytes was identical both under proliferating and differentiating conditions. Assessment of in vivo keratinocyte proliferation at 4 days of age confirmed that VDR ablation did not have a significant effect. There was no difference in the basal expression of markers of keratinocyte differentiation (keratin 1, involucrin, and loricrin) in the keratinocytes isolated from VDR-ablated mice when compared with those isolated from control littermates. Similarly, in vivo expression of these genes was not altered at 4 days of age. When anagen was induced by depilation at 18 days of age, the VDR null mice had a profound impairment in initiation of the hair cycle. These data suggest that the alopecia in the VDR null mice is not attributable to an intrinsic defect in keratinocyte proliferation or differentiation, but rather to an abnormality in initiation of the hair cycle.