Osterix Regulates Tooth Root Formation in a Site-specific Manner

Osterix Regulates Tooth Root Formation in a Site-specific Manner
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DOI:
10.1177/0022034514565647
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发表时间:
2015-03-01
影响因子:
7.6
通讯作者:
Cho, E. S.
Cho, E. S.
中科院分区:
医学1区
文献类型:
--
作者:
Kim, T. H.;Bae, C. H.;Cho, E. S.

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骨和牙本质具有相似的生化组成和生理特性。牙本质是牙齿的主要组成部分,由成牙本质细胞形成;相反,骨由成骨细胞产生。Osterix(Osx)是一种含锌指的转录因子,已被鉴定为成骨细胞分化和骨形成的重要调节因子。然而,很难确定Osx是否在成牙本质细胞分化和牙本质形成中起作用。为了了解Osx在牙本质形成中的作用,我们分析了在Col 1a 1或OC启动子控制下Osx进行组织特异性消融的小鼠。两个独立的Osx条件性基因敲除小鼠表现出类似的磨牙异常。虽然没有表型被发现在这些牙齿的冠,这两个突变株系表现出短磨牙根由于受损的根伸长。此外,这些小鼠的根间牙本质表现出严重的发育不全特征,这可能是由成牙本质细胞分化和牙本质形成中断引起的。这些表型与牙齿发育过程中Osx的时空表达模式密切相关。这些发现表明Osx是通过调节成牙本质细胞的分化、成熟和根伸长来形成根所必需的。累积起来,我们的数据有力地表明,Osx是一个特定于牙根形成的位点调节。
Bone and dentin share similar biochemical compositions and physiological properties. Dentin, a major tooth component, is formed by odontoblasts; in contrast, bone is produced by osteoblasts. Osterix (Osx), a zinc finger-containing transcription factor, has been identified as an essential regulator of osteoblast differentiation and bone formation. However, it has been difficult to establish whether Osx functions in odontoblast differentiation and dentin formation. To understand the role of Osx in dentin formation, we analyzed mice in which Osx was subjected to tissue-specific ablation under the control of either the Col1a1 or the OC promoter. Two independent Osx conditional knockout mice exhibited similar molar abnormalities. Although no phenotype was found in the crowns of these teeth, both mutant lines exhibited short molar roots due to impaired root elongation. Furthermore, the interradicular dentin in these mice showed severe hypoplastic features, which were likely caused by disruptions in odontoblast differentiation and dentin formation. These phenotypes were closely related to the temporospatial expression pattern of Osx during tooth development. These findings indicate that Osx is required for root formation by regulating odontoblast differentiation, maturation, and root elongation. Cumulatively, our data strongly indicate that Osx is a site-specific regulator in tooth root formation.