A role of hematopoiesis-associated transcription factor, Runx1/AML1, in murine skeletal development

造血相关转录因子 Runx1/AML1 在小鼠骨骼发育中的作用

• 批准号: 22790297
• 负责人: HIRAI Takao
• 金额: $ 1.83万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790297/
• 关键词: 生体分子医学; 生体分子; 発生・分化

Runx1(AML1) encodes a hematopoesis-associated transcriptionfactor, the mutations of which are frequently encountered in human leukemia. To investigate the potential role of Runx1 in bone development, therefore, we systematically analyzed the skeleton of the mice in which Runx1 was removed using aCre-loxP system(Prx-Cre ; Runx1^<fl/fl>: Runx1-cKO, fl : floxed allele). In these mice, Runx1should be abolished selectively from the early mesenchyme of the calvaria and the limbprimordium.μCT analysis showed that Runx1-cKO had significantly lower trabecular bone mineral density compared with controls. In addition, bone marrow-derived stromal cells cultures(BMSCs) from 10-week-old Runx1-cKO mice showed that bonemarrow stromal osteogenic colony number relative to total colony forming number(colony-forming unit alkaline phosphatase/CFU-fibroblast) in Runx1-cKO mice wasdecreased in comparison to those observed for the control mice. Taken together, theseresults suggest that Runx1 contributes to the murine osteogenesis.

Runx 1（AML 1）是一种造血相关转录因子，其突变在人类白血病中较为常见。因此，为了研究Runx 1在骨骼发育中的潜在作用，我们使用aCre-loXP系统系统分析了去除Runx 1的小鼠的骨骼（Prx-Cre ; Runx 1 ^<fl/fl>：Runx 1-cKO，fl：floxed等位基因）。在这些小鼠中，Runx 1-cKO应该从颅骨和肢原基的早期间充质中被选择性地消除。μCT分析显示，Runx 1-cKO与对照组相比具有显著更低的骨小梁密度。此外，来自10周龄Runx 1-cKO小鼠的骨髓源性基质细胞培养物（BMSC）显示，与对照小鼠相比，Runx 1-cKO小鼠骨髓基质成骨集落数量相对于总集落形成数量（集落形成单位碱性磷酸酶/CFU成纤维细胞）减少。综上所述，这些结果表明Runx 1参与了小鼠骨生成。

项目成果

A role of hematopoiesis-associated transcription factor, Runx1/AML1, in murine skeletal development

造血相关转录因子 Runx1/AML1 在小鼠骨骼发育中的作用

• 发表时间: 2010
• 作者: 平居貴生;谷内一郎;奥田司
• 通讯作者: 奥田司