TGF-β1 calcium signaling in osteoblasts
TGF-β1 calcium signaling in osteoblasts
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DOI：
10.1002/jcb.21180
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发表时间：
2007-05-15
影响因子：
4
通讯作者：
Tuan, Rocky S.
中科院分区：
文献类型：
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作者：
Nesti, Leon J.;Caterson, E. J.;Tuan, Rocky S.
已知转化生长因子-β 1（TGF-β 1）的作用是通过其与含有丝氨酸/苏氨酸激酶结构域的多种细胞表面受体结合而启动的，所述丝氨酸/苏氨酸激酶结构域用于刺激多种细胞类型中的级联信号传导事件。我们先前已经表明，TGF-β 1和BMP-2处理的原代人成骨细胞（HOB）增强细胞基质粘附。在这篇报道中，我们证明了TGF-β 1能使细胞内Ca 2+浓度[Ca 2 +]（i）迅速、短暂和振荡性升高，这是HOB中细胞粘附增强所必需的，但不会改变Smad蛋白的磷酸化状态。HOB中[Ca 2 +]（i）的这种升高在细胞外钙缺乏时或当细胞用L-型Ca 2+通道阻断剂nifeclipine处理时未观察到，但在用L-型Ca 2+通道激动剂Bay K 8644处理时或在高K+条件下被刺激。用毒胡萝卜素（一种选择性内质网Ca 2+抑制剂）处理细胞后，[Ca 2 +]（i）的升高严重减弱。TGF-β 1促进HOB与组织培养聚苯乙烯的粘附在用尼非利平处理的细胞中也受到抑制。这些数据表明，在成骨细胞功能中，细胞内Ca 2+信号是TGF-β 1信号转导通路的重要第二信使。
Transforming growth factor-beta 1 (TGF-beta 1) action is known to be initiated by its binding to multiple cell surface receptors containing serine/threonine kinase domains that act to stimulate a cascade of signaling events in a variety of cell types. We have previously shown that TGF-beta 1 and BMP-2 treatment of primary human osteoblasts (HOBs) enhances cell-substrate adhesion. In this report, we demonstrate that TGF-beta 1 elicits a rapid, transient, and oscillatory rise in the intracellular Ca2+ concentration, [Ca2+](i), that is necessary for enhancement of cell adhesion in HOBs but does not alter the phosphorylation state of Smad proteins. This rise in [Ca2+](i) in HOB is not observed in the absence of extracellular calcium or when the cells are treated with the L-type Ca2+ channel blocker, nifeclipine, but is stimulated upon treatment with the L-type Ca2+ channel agonist, Bay K 8644, or under high K+ conditions. The rise in [Ca2+](i) is severely attenuated after treatment of the cells with thapsigargin, a selective encloplasmic reticulum Ca2+ PUMP inhibitor. TGF-beta 1 enhancement of HOB adhesion to tissue culture polystyrene is also inhibited in cells treated with nifeclipine. These data suggest that intracellular Ca2+ signaling is an important second messenger of the TGF-beta 1 signal transcluction pathway in osteoblast function.