Cbfa1 promoter regulation in bone cells and its application for regeneration

Cbfa1启动子在骨细胞中的调控及其再生应用

• 批准号: 12557123
• 负责人: NODA Masaki
• 金额: $ 8.51万
• 依托单位: Tokyo Dental and Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12557123/
• 关键词: osteoblast; osteoclast; Cbfa1; BMP; CIZ; signal; bone marrow; progenitor; プロモーター; 転写; 細胞接着; 骨再生; 骨髄幹細胞; Cbfa; 転写因子; プロモーター解析; 軟骨細胞

In this study, we investigated Cbfa1 promoter fragment located up to 1.8 kb up stream to the transcription start site is responsible for the activity of this gene in osteoblastic cells. Further analysis of the 1.8 kb Cbfa1 gene promoter indicated that CIZ can activate Cbfa1 promoter by itself. In addition, in the presence of high levels of BMP signal, Cbfa1 promoter activity is inhibited by the presence of CIZ. Signal interaction analysis indicated that BMP activated Smad action is inhibited by CIZ based on the levels of promoter activations. These data indicated that Cbfa1 is under the control of not only BMP signaling but also by the cell attachment related transcription factor, CIZ. Analysis of the cell transfer experiments using that cells expressing CIZ and Cbfa1 indicated that bone marrow drived progenitor cells could regulate bone marrow and part of the articular catilage.

在这项研究中，我们研究了位于转录起始点上游1.8kb的Cbfa1启动子片段与该基因在成骨细胞中的活性有关。对1.8kb的Cbfa1基因启动子的进一步分析表明，CIZ可以自行激活Cbfa1启动子。此外，在高水平的BMP信号存在下，Cbfa1启动子的活性被CIZ的存在所抑制。信号相互作用分析表明，CIZ根据启动子的激活水平抑制BMP激活的Smad作用。这些数据表明，Cbfa1不仅受BMP信号的调控，而且还受细胞附着相关转录因子CIZ的调控。用表达CIZ和Cbfa1的细胞进行细胞移植实验分析表明，骨髓驱动的祖细胞对骨髓和部分关节腔具有调节作用。

项目成果

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Sekiya,I.、Koopman,P.、Tsuji,K.、Mertin,S.、Harley,V.、Yamada,Y.、Shinomiya,K.、Nifuji,A. 和 Noda,M.：“转录抑制

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Shiraki-Iida T、Iida A、Nabeshima Y、Anazawa H、Nishikawa S、Noda M、Kuro-o M、Nabeshima Y.：“通过腺病毒介导的表达改善 klotho (kl/kl) 小鼠的多种病理生理表型

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Shiraki-Iida T, Iida A,: "Improvement of multiple pathophysiological phenotypes of klotho (kl/kl) mice by adenovirus-mediated expression of the klotho gene"Journal of Gene Med. 2. 233-42 (2000)

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