Human Dermo-1 has attributes similar to twist in early bone development
Human Dermo-1 has attributes similar to twist in early bone development
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DOI：
10.1016/s8756-3282(00)00380-x
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发表时间：
2000-11-01
期刊：
影响因子：
4.1
通讯作者：
Glackin, CA
中科院分区：
文献类型：
--
作者：
Lee, MS;Lowe, G;Glackin, CA
碱性螺旋-环-螺旋(BHLH)转录因子参与细胞谱系的决定和分化。DERMO-L编码的一种bHLH转录因子与另一种bHLH转录因子Twist有广泛的同源性。我们从两个不同的骨质型细胞质文库中克隆并鉴定了人真皮L。在人胚胎和成人组织切片中检测真皮L基因和蛋白的表达。真皮-L在中胚层和外胚层来源的组织中表达。我们进一步检测了Dermo-1/Twist在人类组织和细胞系中的表达。此外，我们还观察了碱性成纤维细胞生长因子在成骨细胞系中的表达，为了评价人成骨细胞转录因子L在成骨细胞代谢中的功能，我们建立了稳定的高表达和低表达人成骨细胞系，并对这些细胞系进行了分析，并与以前发表的转导Twist基因的类似细胞系的数据进行了比较。我们的结果表明，在成骨细胞的形态、骨标记基因表达和对细胞因子的生化反应等方面，L皮肤病引起了与Twist相似的变化，但L皮肤病的表达在调控细胞增殖机制、碱性磷酸酶活性和时间表达模式方面也具有独特的作用。我们推测TWIST和DERMO-L的表达分别使细胞处于成骨细胞样或成骨前细胞样状态，并阻止成骨细胞的过早或异位分化。因此，TWIST和DERMO-L必须依次下调，才能启动成骨细胞分化的级联反应。这些结果表明，在成骨细胞发育过程中，德尔莫-L可能通过与Twist相似但不完全相同的机制来抑制成骨细胞的成熟并维持成骨前细胞的表型。(C)2000，爱思唯尔科学公司。保留所有权利。
Basic helix-loop-helix (bHLH) transcription factors are implicated in cell lineage determination and differentiation. Dermo-l encodes a bHLH transcription factor that shares extensive homology with another bHLH transcription factor, Twist. We have cloned and characterized human Dermo-l from two different hone cytoplasmic DNA (cDNA) libraries. Dermo-l mRNA and protein expression were examined in human embryo and adult tissue sections. Dermo-l is expressed in a subset of mesodermally and ectodermally derived tissues. We further examined expression of Dermo-1/Twist in human tissues and cell lines. In addition, we observed Dermo-l expression in response to basic fibroblast growth factor in osteoblastic cell lines, To evaluate the functionality of the human Dermo-l transcription factor in osteoblast metabolism, we made stable osteoblastic cell lines that over- and underexpress human Dermo-l, These cell lines were analyzed and compared with previously published data of similar cell lines transfected with Twist. Our results demonstrate that Dermo-l caused changes similar to Twist in the osteogenic properties of osteoblastic cells, such as morphology, bone marker gene expression, and biochemical response to cytokines, However, Dermo-l expression also has unique effects in regulating the mechanism of proliferation, on alkaline phosphatase enzyme activity, and in temporal expression patterns. We speculate that expression of Twist and Dermo-l maintains cells in an osteoprogenitor or preosteoblast-like state, respectively, and prevents premature or ectopic osteoblast differentiation. Therefore, Twist and Dermo-l must be sequentially downregulated in order to initiate the cascade of events responsible for osteogenic cell differentiation. These results indicate that, during osteoblast development, Dermo-l may inhibit osteoblast maturation and maintain cells in a preosteoblast phenotype by utilizing mechanisms similar but not identical to those utilized by Twist. (C) 2000 by Elsevier Science Inc. All rights reserved.