p38 mitogen-activated protein kinase regulates osteoblast differentiation through osterix.
p38 mitogen-activated protein kinase regulates osteoblast differentiation through osterix.
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DOI：
10.1210/en.2006-1000
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发表时间：
2007-04
期刊：
影响因子：
4.8
通讯作者：
Xueying Wang;C. H. Goh;Baojie Li
中科院分区：
文献类型：
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作者：
Xueying Wang;C. H. Goh;Baojie Li
p38 MAPK已显示调节成骨细胞分化。用抑制剂或显性阴性突变体抑制该激酶会阻碍成骨细胞分化。然而，这种调节背后的分子机制还没有得到很好的理解。在这里，我们提供的证据表明，p38 MAPK对成骨细胞分化的影响可以通过osterix（Osx），成骨细胞分化所必需的和足够的转录因子介导。抑制p38 MAPK对p53-/-成骨细胞的分化影响最小，而p53-/-成骨细胞具有持续的Osx表达。抑制p38 MAPK下调Osx在蛋白和mRNA水平的表达，但没有参与成骨细胞分化的其他转录因子。更重要的是，这种抑制作用可以显着缓解过度表达Osx的成骨细胞。进一步的实验支持Osx的表达主要受培养液中存在的、成骨细胞分泌的或血清提供的骨形态发生蛋白的调控，p38 MAPK在骨形态发生蛋白诱导的Osx表达中起积极作用。这些发现确定了p38 MAPK调节成骨细胞分化的新机制。
p38 MAPK has been shown to regulate osteoblast differentiation. Inhibition of this kinase with inhibitors or dominant-negative mutant impedes osteoblast differentiation. Yet the molecular mechanism behind this regulation is not well understood. Here we provide evidence that the effect of p38 MAPK on osteoblast differentiation can be mediated by osterix (Osx), a transcription factor necessary and sufficient for osteoblast differentiation. Inhibition of p38 MAPK had minimal effects on differentiation of p53-/- osteoblasts, which had sustained Osx expression. Inhibition of p38 MAPK down-regulated the expression of Osx at both protein and mRNA levels, but not other transcription factors involved in osteoblast differentiation. More importantly, this inhibitory effect could be significantly relieved in osteoblasts overexpressing Osx. Further experiments support that Osx expression is mainly controlled by bone morphogenetic proteins existing in the culture medium, secreted by osteoblasts or provided by serum, and p38 MAPK plays a positive role in bone morphogenetic proteins-induced Osx expression. These findings identify a novel mechanism by which p38 MAPK regulates osteoblast differentiation.