Integrative Study of transcriptional network systems during enchondral ossification

软骨骨化过程中转录网络系统的综合研究

• 批准号: 20229010
• 负责人: YONEDA Toshiyuki
• 金额: $ 136.53万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (S)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20229010/
• 关键词: Sox9; 軟骨分化; 転写制御; Runx2

Enchondral ossification is very unique and complex biological event which is harmoniously and strictly regulated by several growth factors and cytokines. These factors regulate enchondral ossification by controlling intracellular signaling and transcription factors. Transcription factors, Sox9 and Runx2, play essential roles in enchondral ossification. We found that p54^<nrb> couples transcription to mRNA maturation during enchondral ossification by forming transcriptional complex with Sox9. In contrast, Arid5a and Znf219, both of which form transcriptional complex with Sox9, play a role in chondrocyte differentiation in association with Sox9. In addition, we found that Sox9 forms negative-feedback loop with Ihh/Gli signaling for late stage of chondrogenesis by up-regulating PTHrP expression. Furthermore, we identified that a transcription factor, Dmrt2, links Sox9 function to Runx2. Collectively, our findings provide novel insights into molecular basis of enchondral ossification.

软骨骨化是一个非常独特而复杂的生物学过程，它受到多种生长因子和细胞因子的协调和严格调控。这些因子通过控制细胞内信号传导和转录因子来调节内软骨骨化。转录因子Sox 9和Runx 2在软骨骨化中起重要作用。我们发现p54<nrb>通过与Sox 9形成转录复合物，在软骨骨化过程中将转录与mRNA成熟偶联。与此相反，Arid 5a和Znf 219都与Sox 9形成转录复合物，在与Sox 9相关的软骨细胞分化中发挥作用。此外，我们发现Sox 9通过上调PTHrP的表达与Ihh/Gli信号形成负反馈环，用于软骨形成的晚期阶段。此外，我们确定了一个转录因子，Dmrt 2，链接Sox 9功能Runx 2。总的来说，我们的研究结果提供了新的见解的分子基础的enchoniossification。

项目成果

小胞体ストレスセンサーOASISによる骨形成制御.

通过内质网应力传感器 OASIS 控制骨形成。

• 发表时间: 2009
• 作者: 村上智彦;西村理行;米田俊之;池川志郎;和中明生;今泉和則
• 通讯作者: 今泉和則

Cellular ATP Synthesis Mediated by Type III Sodium-dependent Phosphate Transporter Pit-1 Is Critical to Chondrogenesis

• DOI: 10.1074/jbc.m110.148403
• 发表时间: 2011-01-28
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Sugita, Atsushi;Kawai, Shinji;Yoneda, Toshiyuki
• 通讯作者: Yoneda, Toshiyuki

Paraspeckle protein p54nrb links Sox9-mediated transcription with RNA processing during chondrogenesis in mice

• DOI: 10.1172/jci31373
• 发表时间: 2008-09-01
• 期刊: JOURNAL OF CLINICAL INVESTIGATION
• 影响因子: 15.9
• 作者: Hata, Kenji;Nishimura, Riko;Yoneda, Toshiyuki
• 通讯作者: Yoneda, Toshiyuki

Sox9ファミリーはPTHrP の発現誘導を介し内軟骨性骨形成の後期分化を抑制する

Sox9 家族通过诱导 PTHrP 表达抑制软骨内骨形成的晚期分化

• 发表时间: 2008
• 作者: 天野克比古;波多賢二;小野孝一郎;古郷幹彦;西村理行;米田俊之
• 通讯作者: 米田俊之

A Transcription Factor Znf219 Regulates Chondrocyte Differentiation Through Forming Transcription Factory Complex with Sox9

转录因子 Znf219 通过与 Sox9 形成转录工厂复合物来调节软骨细胞分化

• 发表时间: 2008
• 作者: Takigawa Y;Hata K;Muramatsu S;Amano K;Takada K;Matsuda A;Nishimura R;Yoneda T
• 通讯作者: Yoneda T