Stimulation of Sodium‐Dependent Phosphate Transport and Signaling Mechanisms Induced by Basic Fibroblast Growth Factor in MC3T3‐E1 Osteoblast‐like Cells
Stimulation of Sodium‐Dependent Phosphate Transport and Signaling Mechanisms Induced by Basic Fibroblast Growth Factor in MC3T3‐E1 Osteoblast‐like Cells
复制标题
MC3T3-E1 成骨细胞样细胞中碱性成纤维细胞生长因子诱导的钠依赖性磷酸盐转运和信号传导机制的刺激
DOI：
--
复制
发表时间：
2000
影响因子：
6.2
通讯作者：
J. Caverzasio
中科院分区：
文献类型：
--
作者：
A. Suzuki;G. Palmer;J. Bonjour;J. Caverzasio
生理和病理观察表明，碱性成纤维细胞生长因子（bFGF）是成骨细胞分化，特别是颅骨骨化的重要调节因子。实验证据表明，无机磷酸盐（Pi）的运输可能是骨基质钙化的重要功能。在本研究中，我们解决了bFGF对来自小鼠颅骨的MC 3 T3-E1成骨细胞样细胞中Pi转运活性的影响。结果表明，bFGF是这些细胞中钠依赖性Pi转运的有效和选择性刺激剂。由bFGF诱导的Pi转运活性的变化取决于转录和翻译，并且对应于Pi转运系统的最大速度（Vmax）的变化。这些观察结果表明，增强的Pi运输活动，响应bFGF可能会导致插入新合成的Pi转运到质膜。成纤维细胞生长因子受体（FGFR）酪氨酸激酶的选择性抑制剂，SU 5402，钝化由bFGF诱导的Pi运输的刺激。它还阻止了bFGF诱导的蛋白酪氨酸磷酸化的增加，包括FGFR-1，FGFR-2，磷脂酶C-γ（PLC-γ）和Shc的磷酸化以及Grb 2/Sos信号复合物的募集。此外，bFGF诱导丝裂原活化蛋白（MAP）激酶细胞外信号调节激酶（ERK）和p38的活化，SU 5402可阻止这种效应。蛋白激酶C（PKC）抑制剂calphostin C和PKC下调抑制bFGF对Pi转运的刺激作用。ERK和p38 MAP激酶的选择性抑制剂略微降低了这种细胞反应，在最高浓度的p38 MAP激酶抑制剂下观察到显著效果。总之，本研究的结果表明，bFGF选择性地刺激颅骨源性成骨细胞中的Pi转运。负责这种效应的主要信号传导机制涉及PLC-γ的酪氨酸磷酸化和PKC的活化，可能有p38 MAP激酶途径的贡献。
Physiological and pathological observations indicate that basic fibroblast growth factor (bFGF) is an important regulator of osteoblastic cell differentiation and in particular of cranial ossification. Experimental evidence suggests that inorganic phosphate (Pi) transport could be an important function of bone matrix calcification. In the present study, we address the influence of bFGF on Pi transport activity in MC3T3‐E1 osteoblast‐like cells derived from mouse calvaria. The results indicate that bFGF is a potent and selective stimulator of sodium‐dependent Pi transport in these cells. The change in Pi transport activity induced by bFGF depends on transcription and translation and corresponds to a change in the maximum velocity of the Pi transport system (Vmax). These observations suggest that enhanced Pi transport activity in response to bFGF may result from insertion of newly synthesized Pi transporters into the plasma membrane. A selective inhibitor of fibroblast growth factor receptor (FGFR) tyrosine kinase, SU5402, blunted the stimulation of Pi transport induced by bFGF. It also prevented the increase in protein tyrosine phosphorylation induced by bFGF, including phosphorylation of FGFR‐1, FGFR‐2, phospholipase C‐γ (PLC‐γ), and Shc as well as the recruitment of the Grb2/Sos signaling complex. In addition, bFGF‐ induced the activation of the mitogen‐activated protein (MAP) kinases extracellular signal–regulated kinase (ERK) and p38, effects that were prevented by SU5402. Both the protein kinase C (PKC) inhibitor calphostin C and PKC down‐regulation suppressed the stimulatory effect of bFGF on Pi transport. Selective inhibitors of ERK and p38 MAP kinases slightly reduced this cellular response with a significant effect observed with the highest concentration of the p38 MAP kinase inhibitor. In conclusion, the results of this study indicate that bFGF selectively stimulates Pi transport in calvaria‐derived osteoblastic cells. The main signaling mechanism responsible for this effect involves tyrosine phosphorylation of PLC‐γ and activation of PKC, with a possible contribution of the p38 MAP kinase pathway.
影响因子：
4.6
作者：
A. Wanaka;J. Milbrandt;Eugene M. Johnson
通讯作者：
A. Wanaka;J. Milbrandt;Eugene M. Johnson