The bone-related Zn finger transcription factor Osterix promotes proliferation of mesenchymal cells

The bone-related Zn finger transcription factor Osterix promotes proliferation of mesenchymal cells
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DOI:
10.1016/j.gene.2005.08.021
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发表时间:
2006-01-17
期刊:
影响因子:
3.5
通讯作者:
Choi, JY
Choi, JY
中科院分区:
生物学3区
文献类型:
--
作者:
Kim, YJ;Kim, HN;Choi, JY

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Osterix 是一种与骨相关的转录因子,在 Runx2 下游发挥遗传作用,Runx2 控制成骨细胞的生长和分化。在这里,我们评估了 Osterix 在通常不属于成骨谱系的间充质细胞中的生物学功能。通过分析骨表型相关标记物的基因表达谱以及测量骨结节形成和细胞增殖,检查表达外源 Osterix 的稳定转染的 NIH3T3 成纤维细胞转化为成骨细胞的能力。 Osterix 的强制表达会刺激骨桥蛋白基因表达,但不会刺激其他骨相关标记物的表达或活性,包括 1 型胶原、碱性磷酸酶、骨钙素或骨粘连蛋白。此外,稳定表达 Osterix 的细胞不会诱导骨结节形成。引人注目的是,表达 Osterix 的多克隆和单克隆细胞均表现出增殖增强。总的来说,这些结果表明 Osterix 不足以建立成骨谱系承诺,这可能是由于 Osterix 促进细胞生长的能力。我们提出,未定型间充质细胞的成骨转化需要 Osterix 上游或与 Osterix 平行运行的调控途径。 (c) 2005 Elsevier B.V. 保留所有权利。
Osterix is a bone-related transcription factor that functions genetically downstream of Runx2, which controls both growth and differentiation in osteoblasts. Here we assessed the biological function of Osterix in mesenchymal cells that are not normally committed to the osteogenic lineage. Stably transfected NIH3T3 fibroblasts that express exogenous Osterix were examined for their ability to convert into osteoblastic cells by analyzing gene expression profiles of bone phenotype related markers, as well as by measuring bone nodule formation and cell proliferation. Forced expression of Osterix stimulates osteopontin gene expression but not the expression or activity of other bone-related markers, including collagen type 1, alkaline phosphatase, osteocalcin, or osteonectin. Moreover, cells stably expressing Osterix do not induce bone nodule formation. Strikingly, both polyclonal and monoclonal cells expressing Osterix exhibit enhanced proliferation. Collectively, these results indicate that Osterix is insufficient to establish osteogenic lineage commitment, perhaps due to the ability of Osterix to promote cell growth. We propose that regulatory pathways operating upstream of or in parallel with Osterix are required for osteogenic conversion of uncommitted mesenchymal cells. (c) 2005 Elsevier B.V. All rights reserved.