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首页> 外文期刊>Journal of Cellular Physiology >Sox9, a key transcription factor of bone morphogenetic protein-2-induced chondrogenesis, is activated through BMP pathway and a CCAAT box in the proximal promoter.
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Sox9, a key transcription factor of bone morphogenetic protein-2-induced chondrogenesis, is activated through BMP pathway and a CCAAT box in the proximal promoter.

机译：Sox9,一个关键的转录因子的骨头形态形成protein-2-induced软骨形成,通过BMP激活通路和CCAAT箱子吗在近端启动子。

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摘要

Mouse embryonic fibroblasts (MEFs) can be differentiated into fully functional chondrocytes in response to bone morphogenetic protein-2 (BMP-2). The expression of Sox9, a critical transcription factor for the multiple steps of chondrogenesis, has been reported to be upregulated during this process. But the molecular mechanisms by which BMP-2 promotes chondrogenesis still remain largely unknown. The aim of the present study was therefore to investigate the underlying mechanism. In the MEFs, BMP-2 efficiently induced Sox9 expression along with chondrogenic differentiation in a time- and dose-dependent manner. SB203580, a specific inhibitor for p38 pathway, blocked BMP-2-induced chondrogenic differentiation as well as Sox9 expression and its transactivation of downstream genes. Forced expression of Smad6, a natural antagonist for BMP/Smad pathway, only inhibited Sox9 protein function without rendering any effects on its mRNA expression. A CCAAT box was identified in Sox9 promoter as the cis-elements responsible for BMP-2 stimulation. This study provides insight into the mechanisms underlying BMP-2-regulated Sox9 expression and activity in MEFs, and suggests differential roles of BMP-2/p38 and BMP-2/Smad pathways in modulating the function of Sox9 during chondrogenesis.
机译：小鼠胚胎成纤维细胞(mef)分化为功能齐全的软骨细胞在对骨形成protein-2回应(BMP-2)。转录因子的多个步骤软骨形成,据报道在这个过程中调节。BMP-2促进分子机制软骨形成很大程度上仍未知。因此,本研究的目标调查潜在的机制。mef, BMP-2有效诱导表达Sox9随着chondrogenic分化时间和剂量依赖性的方式。具体p38通路的抑制剂,屏蔽BMP-2-induced chondrogenic分化为Sox9表达式及其transactivation的下游基因。自然拮抗剂BMP / Smad途径,只有抑制Sox9蛋白功能没有呈现任何影响其mRNA的表达。被发现在Sox9启动子cis-elements负责BMP-2刺激。本研究提供了洞察机制和潜在BMP-2-regulated Sox9表达式mef活动,表明微分作用BMP-2 / p38和BMP-2 / Smad通路调制期间Sox9的功能软骨形成。

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