Proliferation and differentiation of human osteoblastic cells associated with differential activation of MAP kinases in response to epidermal growth factor, hypoxia, and mechanical stress in vitro
Proliferation and differentiation of human osteoblastic cells associated with differential activation of MAP kinases in response to epidermal growth factor, hypoxia, and mechanical stress in vitro
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DOI：
10.1006/bbrc.1998.9151
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发表时间：
1998-08-19
影响因子：
3.1
通讯作者：
Watanabe, M
中科院分区：
文献类型：
--
作者：
Matsuda, N;Morita, N;Watanabe, M
为了阐明从环境压力到细胞结果通过丝裂原活化蛋白激酶（MAPK）激活的途径的特异性，我们研究了培养的人成骨细胞牙周韧带（PDL）细胞对表皮生长因子（EGF），缺氧和机械应力的反应，在细胞增殖，分化和相关的三种不同类型的MAPK激活。细胞增殖促进在10 ng/ml的EGF的存在下，或在缺氧条件下（5%O2），而它被抑制的周期性拉伸（9%应变，6个周期/分钟），这是用来作为一个模型的机械应力。相反，碱性磷酸酶活性，成骨细胞分化的细胞的标志物，增加了周期性拉伸，但EGF和缺氧下降。PDL细胞对EGF或缺氧的促有丝分裂反应与细胞外相关激酶（ERK）1/2的选择性磷酸化和激活有关，而在机械牵张负荷的细胞中观察到c-Jun N-末端激酶（JNK）的磷酸化和激活。而p38蛋白则无此变化。这些结果表明，增殖和成骨细胞分化的PDL细胞的应激反应的变化选择性介导的ERK 1/2和JNK，分别，这两种途径之间的平衡决定了细胞的命运。(C)北京：科学出版社.
In an attempt to elucidate the specificity of pathways from environmental stress to cellular outcome via mitogen activated protein kinases (MAPKs) activation, we examined the responsiveness of cultured human osteoblastic periodontal ligament (PDL) cells to epidermal growth factor (EGF), hypoxia, and mechanical stress, in terms of cell proliferation, differentiation, and associated activation of three different types of MAPK. Cell proliferation was promoted in the presence of 10ng/ml of EGF or in hypoxic conditions (5% O2), whereas it was inhibited by cyclic stretch (9% strain, 6 cycles/min), which was used as a model of mechanical stress. Conversely, the alkaline phosphatase activity, a marker for osteoblastic differentiation of the cells, was increased by cyclic stretch but decreased by EGF and hypoxia. The mitogenic response of PDL cells to EGF or hypoxia was associated with the selective phosphorylation and activation of extracellular-related kinase (ERK) 1/2, while phosphorylation and activation of c-Jun N-terminal kinase (JNK) was observed in mechanical stretch loaded cells. No such changes were seen in p38 protein. These findings suggested that stress-responsive changes in proliferation and osteoblastic differentiation of PDL cells are selectively mediated by ERK 1/2 and by JNK, respectively, and that a balance between these two pathways determines the cell fate. (C) 1998 Academic Press.