Activation of p38 mitogen-activated protein kinase is required for osteoblast differentiation
Activation of p38 mitogen-activated protein kinase is required for osteoblast differentiation
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DOI：
10.1210/en.2002-220863
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发表时间：
2003-05-01
期刊：
影响因子：
4.8
通讯作者：
Li, BJ
中科院分区：
文献类型：
--
作者：
Hu, YY;Chan, E;Li, BJ
p38 MAPK是MAPKs的保守亚家族，参与炎症反应、应激反应、细胞生长和存活以及多种细胞类型的分化。在这份报告中，我们证明了p38 MAPK在成骨细胞分化中发挥了重要作用，使用原代颅骨成骨细胞，骨髓成骨细胞培养，和小鼠细胞系，MC 3 T3-E1。我们发现p38 MAPK在颅骨成骨细胞分化过程中与细胞外信号调节激酶（ERK）一起被沿着激活。当用特异性抑制剂抑制p38 MAPK时，分化标志物如碱性磷酸酶和矿物质沉积的表达显著降低。表达显性负性p38 MAPK的MC 3 T3-E1细胞也显示出ALP和矿物质沉积延迟的迹象。骨髓骨前体细胞的分化也受到p38 MAPK抑制剂的阻碍，这是由相同的标志物证明的。然而，在颅骨成骨细胞和骨髓骨祖细胞中观察到的抑制作用可以部分地被骨形态发生蛋白-2所取代。用特定的药物抑制ERK并不显著影响成骨细胞的分化，即使ERK 1/2也在成骨细胞分化过程中被激活。这些结果共同表明，p38 MAPK，而不是ERK，是成骨细胞分化所必需的。
p38 MAPK is a conserved subfamily of MAPKs involved in inflammatory response, stress response, cell growth and survival, as well as differentiation of a variety of cell types. In this report we demonstrated that p38 MAPK played an important role in osteoblast differentiation using primary calvarial osteoblast, bone marrow osteoprecursor culture, and a murine cell line, MC3T3-E1. We found that p38 MAPK was activated as calvarial osteoblast differentiates along with extracellular signal-regulated kinases (ERKs). When p38 MAPK is inhibited with a specific inhibitor, the expression of differentiation markers, such as alkaline phosphatase and mineral deposition, were significantly reduced. MC3T3-E1 cells expressing dominant negative p38 MAPK also displayed signs of delay in ALP and mineral deposition. Differentiation of the bone marrow osteoprecursors was also impeded by the p38 MAPK inhibitor, justified by the same markers. Yet the inhibitory effects observed in calvarial osteoblasts and bone marrow osteoprogenitor cells could be partially prevailed by bone morphogenetic protein-2. Inhibition of ERKs with a specific drug did not significantly affect osteoblast differentiation even though ERK1/2 were also activated during osteoblast differentiation. These results taken together indicate that p38 MAPK, but not ERKs, is necessary for osteoblast differentiation.