1alpha,25(OH)2-vitamin D3 membrane-initiated calcium signaling modulates exocytosis and cell survival.
1alpha,25(OH)2-vitamin D3 membrane-initiated calcium signaling modulates exocytosis and cell survival.
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1α,25(OH)2-维生素 D3 膜启动的钙信号传导调节胞吐作用和细胞存活。
DOI：
10.1016/j.jsbmb.2006.11.002
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Zanello,LauraP
中科院分区：
文献类型：
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作者：
Xiaoyu,Zhang;Payal,Biswas;Melissa,Owraghi;Zanello,LauraP
1α，25（OH）2-维生素D3（1，25 D）被认为是一种骨合成代谢激素。1，25 D的作用导致骨形成，涉及基因的反式激活，一方面，和细胞质信号的调制，另一方面。在这两种情况下，似乎都需要功能性维生素D受体（VDR）。在这里，我们研究了1，25 D刺激的钙信号，它起始于细胞膜，导致骨材料的胞吐作用，并增加成骨细胞的存活。我们发现，在成骨细胞ROS 17/2.8细胞中，1，25 D诱导胞吐作用的快速发生与细胞质钙离子的增加有关。此外，我们发现，细胞质钙浓度的升高涉及1，25 D通过Akt激活ROS 17/2.8细胞和非成骨细胞CV-1细胞中的抗凋亡作用。在这两种情况下，1，25 D刺激的细胞内钙离子升高部分是由于L-型Ca 2+通道的激活。我们的结论是，1，25 D骨合成代谢的影响，涉及增加细胞内Ca 2+浓度成骨细胞可以解释在两个水平。在单细胞水平，1，25 D促进Ca 2+依赖的胞吐活动。在组织水平，1，25 D通过Ca 2+依赖性Akt途径保护成骨细胞免于凋亡。我们的研究有助于了解以骨形成和矿化减少为特征的骨疾病的分子基础。
1α,25(OH)2-vitamin D3(1,25D) is considered a bone anabolic hormone. 1,25D actions leading to bone formation involve gene transactivation, on one hand, and modulation of cytoplasmic signaling, on the other. In both cases, a functional vitamin D receptor (VDR) appears to be required. Here we study 1,25D-stimulated calcium signaling that initiates at the cell membrane and leads to exocytosis of bone materials and increased osteoblast survival. We found that rapid 1,25D-induction of exocytosis couples to cytoplasmic calcium increase in osteoblastic ROS 17/2.8 cells. In addition, we found that elevation of cytoplasmic calcium concentration is involved in 1,25D anti-apoptotic effects via Akt activation in ROS 17/2.8 cells and non-osteoblastic CV-1 cells. In both cases, 1,25D-stimulated elevation of intracellular calcium is due in part to activation of L-type Ca2+channels. We conclude that 1,25D bone anabolic effects that involve increased intracellular Ca2+concentration in osteoblasts can be explained at two levels. At the single-cell level, 1,25D promotes Ca2+-dependent exocytotic activities. At the tissue level, 1,25D protects osteoblasts from apoptosis via a Ca2+-dependent Akt pathway. Our studies contribute to the understanding of the molecular basis of bone diseases characterized by decreased bone formation and mineralization.