Crosstalk between tyrosine kinase receptors, GSK3 and BMP2 signaling during osteoblastic differentiation of human mesenchymal stem cells
Crosstalk between tyrosine kinase receptors, GSK3 and BMP2 signaling during osteoblastic differentiation of human mesenchymal stem cells
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DOI：
10.1016/j.mce.2013.09.018
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发表时间：
2014-01-25
影响因子：
4.1
通讯作者：
Caverzasio, Joseph
中科院分区：
文献类型：
--
作者：
Biver, Emmanuel;Thouverey, Cyril;Caverzasio, Joseph
骨形态发生蛋白（BMPs）促进间充质干细胞（MSC）成骨分化，而血小板衍生生长因子（PDGF）和成纤维细胞生长因子（FGF）通过受体酪氨酸激酶（RTK）激活其增殖。在人MSC（HMSC）中研究PDGF或FGF受体信号传导途径对BMP 2诱导的成骨细胞分化的影响。抑制PDGF或/和FGF受体可增强BMP 2诱导的碱性磷酸酶（ALP）活性、Osterix、ALP和骨唾液蛋白的表达以及基质钙化。这些作用与增加的Smad-1活性相关，表明促有丝分裂因子干扰HMSC分化中的Smad信号传导。RTK通过PI 3 K/Akt通路激活MAPK并抑制GSK 3。生化分析表明MAPK、JNK和GSK 3是BMP诱导HMSC向成骨细胞分化的信号分子。这些观察结果强调了BMP 2的成骨作用是由通过RTK起作用的促有丝分裂因子调节的。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Bone morphogenic proteins (BMPs) promote mesenchymal stem cell (MSC) osteogenic differentiation, whereas platelet derived growth factor (PDGF) and fibroblast growth factor (FGF) activate their proliferation through receptors tyrosine kinase (RTK). The effects of PDGF or FGF receptor signaling pathway on BMP2-induced osteoblastic differentiation was investigated in human MSC (HMSC). Inhibition of PDGF or/and FGF receptors enhanced BMP2-induced alkaline phosphatase (ALP) activity, expression of Osterix, ALP and Bone sialoprotein, and matrix calcification. These effects were associated with increased Smad-1 activity, indicating that mitogenic factors interfere with Smad signaling in HMSC differentiation. RTK activate MAPK and inhibit GSK3 through the PI3K/Akt pathway. Biochemical analysis indicated that MAPK JNK and GSK3 especially are potential signaling molecules regulating BMP-induced osteoblastic HMSC differentiation. These observations highlight that the osteogenic effects of BMP2 are modulated by mitogenic factors acting through RTK. (C) 2013 Elsevier Ireland Ltd. All rights reserved.