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首页> 外文期刊>Molecular and Cellular Biology >The Zinc Finger Transcription Factor Gli2 Mediates Bone Morphogenetic Protein 2 Expression in Osteoblasts in Response to Hedgehog Signaling
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The Zinc Finger Transcription Factor Gli2 Mediates Bone Morphogenetic Protein 2 Expression in Osteoblasts in Response to Hedgehog Signaling

机译：锌指转录因子Gli2介导对刺猬信号的成骨细胞骨形态发生蛋白2表达。

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Bone morphogenetic protein 2 (BMP-2) plays a critical role in osteoblast function. In Drosophila, Cubitus interruptus (Ci), which mediates hedgehog signaling, regulates gene expression of dpp, the ortholog of mammalian BMP-2. Null mutation of the transcription factor Gli2, a mammalian homolog of Ci, results in severe skeletal abnormalities in mice. We hypothesize that Gli2 regulates BMP-2 gene transcription and thus osteoblast differentiation. In the present study, we show that overexpression of Gli2 enhances BMP-2 promoter activity and mRNA expression in osteoblast precursor cells. In contrast, knocking down Gli2 expression by Gli2 small interfering RNA or genetic ablation of the Gli2 gene results in significant inhibition of BMP-2 gene expression in osteoblasts. Promoter analyses, including chromatin immunoprecipitation and electrophoretic mobility shift assays, provided direct evidence that Gli2 physically interacts with the BMP-2 promoter. Functional studies showed that Gli2 is required for osteoblast maturation in a BMP-2-dependent manner. Finally, Sonic hedgehog (Shh) stimulates BMP-2 promoter activity and osteoblast differentiation, and the effects of Shh are mediated by Gli2. Taken together, these results indicate that Gli2 mediates hedgehog signaling in osteoblasts and is a powerful activator of BMP-2 gene expression, which is required in turn for normal osteoblast differentiation.
机译：骨形态发生蛋白2（BMP-2）在成骨细胞功能中起关键作用。在果蝇中，介导刺猬信号的Cubitus interruptus（Ci）调节哺乳动物BMP-2直系同源物 dpp 的基因表达。转录因子Gli2（Ci的哺乳动物同系物）的空突变导致小鼠中严重的骨骼异常。我们假设Gli2调节BMP-2基因的转录，从而调节成骨细胞的分化。在本研究中，我们表明，Gli2的过表达增强了成骨细胞前体细胞中的BMP-2启动子活性和mRNA表达。相反，通过Gli2小干扰RNA敲低Gli2表达或遗传消融Gli2基因会显着抑制成骨细胞中BMP-2基因的表达。启动子分析，包括染色质免疫沉淀和电泳迁移率迁移分析，提供了直接证据，证明Gli2与BMP-2启动子发生物理相互作用。功能研究表明，Gli2是成骨细胞成熟所需的BMP-2依赖方式。最后，声波刺猬（Shh）刺激BMP-2启动子活性和成骨细胞分化，Shh的作用由Gli2介导。综上所述，这些结果表明，Gli2介导成骨细胞中的刺猬信号，并且是BMP-2基因表达的强大激活剂，而这又是正常成骨细胞分化所必需的。

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