Genetic and molecular control of osterix in skeletal formation.
Genetic and molecular control of osterix in skeletal formation.
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DOI：
10.1002/jcb.24439
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发表时间：
2013-05
影响因子：
4
通讯作者：
Zhou, Xin
中科院分区：
文献类型：
--
作者：
Sinha, Krishna M.;Zhou, Xin
成骨细胞分化是一个多步骤的过程，间充质细胞分化为包括骨细胞在内的成骨细胞系细胞。Osterix(OSX)是一种成骨细胞特异性转录因子，在成骨前细胞分化为成熟成骨细胞和成骨细胞的过程中激活一系列基因。OSX在骨形成的遗传程序和骨稳态中的重要作用已经得到了很好的证实。OSX突变胚胎不形成骨骼，也不能表达成骨细胞特异性标记基因。OSX在小鼠出生后失活会导致多种骨骼表型，包括缺乏新骨形成，矿化软骨缺乏吸收，骨细胞成熟和功能缺陷。由于OSX是骨骼形成的主要效应者，OSX的研究在过去的五到七年中获得了势头，并暗示OSX在牙齿形成和骨折愈合中具有重要作用。这篇综述概述了小鼠的遗传学研究，这些研究确立了OSX在骨和牙齿形成以及在骨折愈合中的重要作用。我们还讨论了在转录网络、信号通路和表观遗传调控下调控OSX表达的最新进展。最后，我们总结了OSX在成骨细胞分化过程中通过其靶基因表达中的蛋白质-蛋白质相互作用对其转录活性进行正向和负向调控的重要发现。特别是，组蛋白去甲基酶NO66是一种负性调节OSX活性的OSX相互作用蛋白，这为进一步研究OSX靶基因在成骨细胞分化和成熟过程中的表观遗传控制开辟了新的途径。
Osteoblast differentiation is a multi-step process where mesenchymal cells differentiate into osteoblast lineage cells including osteocytes. Osterix (Osx) is an osteoblast-specific transcription factor which activates a repertoire of genes during differentiation of preosteoblasts into mature osteoblasts and osteocytes. The essential role of Osx in the genetic program of bone formation and in bone homeostasis is well established. Osx mutant embryos do not form bone and fail to express osteoblast-specific marker genes. Inactivation of Osx in mice after birth causes multiple skeletal phenotypes including lack of new bone formation, absence of resorption of mineralized cartilage, and defects in osteocyte maturation and function. Since Osx is a major effector in skeletal formation, studies on Osx gained momentum over the last five-seven years and implicated its important function in tooth formation as well as in healing of bone fractures. This review outlines mouse genetic studies that establish the essential role of Osx in bone and tooth formation as well as in healing of bone fractures. We also discuss the recent advances in regulation of Osx expression which is under control of a transcriptional network, signaling pathways, and epigenetic regulation. Finally we summarize important findings on the positive and negative regulation of Osx’s transcriptional activity through protein-protein interactions in expression of its target genes during osteoblast differentiation. In particular, the identification of the histone demethylase NO66 as an Osx-interacting protein which negatively regulates Osx activity opens further avenues in studying epigenetic control of Osx target genes during differentiation and maturation of osteoblasts.
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影响因子：
4.8
作者：
Jose Ortuno, Maria;Ruiz-Gaspa, Silvia;Ventura, Francesc
通讯作者：
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DOI：
10.1159/000151453
发表时间：
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期刊：
Cells, tissues, organs
影响因子：
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作者：
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