The analysis of the network transcription regulation by the IKK・r in the tooth differentiation and development.

IKK·r在牙齿分化发育中的网络转录调控分析。

• 批准号: 17592125
• 负责人: KIKUIRI Takashi
• 金额: $ 2.37万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17592125/
• 关键词: tooth differentiation and development; transcription regulation; tooth germ; IKK-γ; NF-κB; NEMO gene; siRNA; organ culture; 歯学; 発生・分化; 遺伝子; ゲノム

The tooth development is adjusted by the appearance of various genes and growth factors such as cytokines, and a complex signal network is clarified to the differentiation and the formation of teeth. However, details of all mechanisms in the tooth development are not clarified. In this research, we forced the IKK-y signaling in the mechanism of the teeth development.1. Confirmation of mRNA appearance of IKK-γ in the early stage of teeth development The tooth germ of each stage and the surrounding tissue were removed from mouse's jaw bone and cultured. We did the in situ hybridization of IKK-γ in order to confirm the appearance of IKK-y expression in each tooth germ stage. As a result, it was confirmed that IKK-γ strongly appeared in the early stage of the tooth germ.2. Using siRNA to knock downs of IKK-γ expressionThe tooth germ of each stage and the surrounding tissue including the dental germ were removed from mouse's jawbone, and the organ culture was done. siRNA of IKK-γ was injected by the process of the organ culture, and a morphologic change in the formation of the tooth germ was examined. As a result, not only the growth of the tooth germ but also the growth of the lower jaw bone was spurred by the siRNA.3. Explore of the transcription factorsThe appearance of NF-κB that was one of the transcription factors was suppressed in the group of the siRNA of IKK-γ. As NF-κB plays a key role in cell differentiation, apoptosis and viral infection, it is necessity for examining the cell signaling of the activation of IKK-γ and NF-κB in the tooth development.Those results suggest that IKK-γ is associated with the formation of teeth and the jaw bones. Our data suggested that IKK-γ is an important signal to reveal the mechanism of the teeth development and the differentiation.

牙齿的发育受到各种基因和细胞因子等生长因子的出现的调节，阐明了牙齿分化和形成的复杂信号网络。然而，牙齿发育的所有机制的细节尚不清楚。在这项研究中，我们将IKK-y信号强加到牙齿发育的机制中。1．牙齿发育早期IKK-γ mRNA出现的确认从小鼠颌骨中取出各个阶段的牙胚及其周围组织并进行培养。我们对 IKK-γ 进行了原位杂交，以确认 IKK-y 在每个牙胚阶段的表达情况。结果证实IKK-γ在牙胚早期强烈出现。2．利用siRNA敲低IKK-γ的表达从小鼠颌骨中取出各阶段的牙胚及包括牙胚在内的周围组织，并进行器官培养。通过器官培养过程注射IKK-γ的siRNA，并检查牙胚形成的形态变化。结果，siRNA不仅刺激了牙胚的生长，还刺激了下颌骨的生长。3。转录因子的探讨在IKK-γ的siRNA组中，作为转录因子之一的NF-κB的出现受到抑制。由于NF-κB在细胞分化、细胞凋亡和病毒感染中发挥着关键作用，因此有必要研究牙齿发育过程中IKK-γ和NF-κB激活的细胞信号传导。这些结果表明IKK-γ与牙齿和颌骨的形成有关。我们的数据表明IKK-γ是揭示牙齿发育和分化机制的重要信号。