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首页> 外文期刊>Journal of cellular biochemistry. >Novel target genes of RUNX2 transcription factor and 1,25-dihydroxyvitamin D3
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Novel target genes of RUNX2 transcription factor and 1,25-dihydroxyvitamin D3

机译：RUNX2转录因子和1,25-二羟基维生素D3的新型靶基因

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摘要

The RUNX2 transcription factor is indispensable for skeletal development and controls bone formation by acting as a signaling hub and transcriptional regulator to coordinate target gene expression. A signaling partner of RUNX2 is the nuclear vitamin D receptor (VDR) that becomes active when bound by its ligand 1,25-dihydroxyvitamin D3 (VD3). RUNX2 and VDR unite to cooperatively regulate the expression of numerous genes. In this study, we overexpressed RUNX2 in NIH3T3 fibroblasts concomitantly treated with VD3 and show that RUNX2 alone, or in combination with VD3, failed to promote an osteoblastic phenotype in NIH3T3 cells. However, the expression of numerous osteoblast-related genes was up-regulated by RUNX2 and large-scale gene expression profiling using microarrays identified over 800 transcripts that displayed a twofold of greater change in expression in response to RUNX2 overexpression or VD3 treatment. Functional analysis using gene ontology (GO) revealed GO terms for ossification, cellular motility, biological adhesion, and chromosome organization were enriched in the pool of genes regulated by RUNX2. For the set of genes whose expression was modulated by VD3, the GO terms response to hormone stimulus, chemotaxis, and metalloendopeptidase activity where overrepresented. Our study provides a functional insight into the consequences of RUNX2 overexpression and VD3 treatment in NIH3T3 cells in addition to identifying candidate genes whose expression is controlled by either factor individually or through their functional cooperation. J. Cell. Biochem. 115: 1594-1608, 2014.
机译：RUNX2转录因子对于骨骼发育是必不可少的，它通过充当信号枢纽和转录调节剂来协调靶基因的表达来控制骨骼的形成。 RUNX2的信号传递伙伴是核维生素D受体（VDR），当与它的配体1,25-二羟基维生素D3（VD3）结合时，它就具有活性。 RUNX2和VDR联合起来共同调节众多基因的表达。在这项研究中，我们在同时用VD3处理的NIH3T3成纤维细胞中过表达RUNX2，并显示单独的RUNX2或与VD3组合不能在NIH3T3细胞中促进成骨细胞表型。但是，许多成骨细胞相关基因的表达被RUNX2上调，并且使用微阵列进行大规模基因表达谱分析，鉴定了800多个转录物，这些转录物响应RUNX2过表达或VD3处理而表现出两倍大的表达变化。使用基因本体论（GO）进行的功能分析显示，GO的骨化，细胞运动，生物粘附和染色体组织术语丰富了RUNX2调控的基因库。对于表达受VD3调节的那组基因，GO代表了对激素刺激，趋化性和金属内肽酶活性的反应，而这些反应过高。我们的研究提供了功能性洞察力，用于研究NIH3T3细胞中RUNX2过表达和VD3处理的后果，此外还可以识别其表达受单个因子或通过其功能合作控制的候选基因。 J.细胞。生化。 115：1594-1608，2014。

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