Transcriptional Regulation of Osteoblasts
Transcriptional Regulation of Osteoblasts
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DOI：
10.1159/000151747
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发表时间：
2009-01-01
影响因子：
2.7
通讯作者：
Jiang, Di
中科院分区：
文献类型：
--
作者：
Franceschi, Renny T.;Ge, Chunxi;Jiang, Di
成骨细胞从间充质前体细胞的分化需要一系列的细胞命运的决定控制的转录因子的层次。这些包括RUNX2，Osterix（OSX），ATF4和大量的核共调节子。在骨发育过程中，初始RUNX2表达与间充质凝聚的形成相一致，并且先于软骨生成和成骨谱系的分支。鉴于其在骨骼发育中的核心作用，RUNX2受到各种控制也就不足为奇了。这些包括翻译后修饰，特别是磷酸化，以及与辅助核因子的相互作用。RUNX2调节的具体例子包括ERK/MAP激酶途径的磷酸化和与DLX5的相互作用。RUNX2通过脯氨酸/丝氨酸/苏氨酸结构域中关键丝氨酸残基的磷酸化来调节。在体内，成骨细胞中组成型活性MAP激酶的转基因表达加速骨骼发育，而显性负性MAPK以RUNX2依赖的方式延缓发育。DLX5-RUNX2复合物可以在成骨细胞中检测到，这种相互作用在维持骨唾液酸蛋白基因的成骨细胞特异性表达中起关键作用。这些研究使我们开始理解当间充质祖细胞向成骨细胞谱系发展时，微调骨形成所必需的复杂机制。版权所有（C）2008 S. Karger AG，巴塞尔
The differentiation of osteoblasts from mesenchymal precursors requires a series of cell fate decisions controlled by a hierarchy of transcription factors. These include RUNX2, Osterix (OSX), ATF4 and a large number of nuclear coregulators. During bone development, initial RUNX2 expression coincides with the formation of mesenchymal condensations and precedes the branching of chondrogenic and osteogenic lineages. Given its central role in bone development, it is not surprising that RUNX2 is subject to a variety of controls. These include posttranslational modification, especially phosphorylation, and interactions with accessory nuclear factors. Specific examples of RUNX2 regulation to be reviewed include phosphorylation by the ERK/MAP kinase pathway and interactions with DLX5. RUNX2 is regulated via phosphorylation of critical serine residues in the proline/serine/ threonine domain. In vivo, the transgenic expression of constitutively active MAP kinase in osteoblasts accelerated skeletal development, while a dominant-negative MAPK retarded development in a RUNX2-dependent manner. DLX5-RUNX2 complexes can be detected in osteoblasts and this interaction plays a critical role in maintaining osteoblast-specific expression of the bone sialoprotein gene. These studies allow us to begin understanding the complex mechanisms necessary to fine-tune bone formation as mesenchymal progenitors progress down the osteoblast lineage. Copyright (C) 2008 S. Karger AG, Basel