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

RUNX1(AML1)编码一种与造血相关的转录因子，其突变常见于人类白血病。因此，为了研究RUNX1在骨发育中的潜在作用，我们使用ALARE-loxP系统(PRX-CRE；RUNX1^&lt；fl/fl&gt；：RUNX1-CKO，fl：Floated等位基因)对RUNX1被移除的小鼠的骨骼进行了系统的分析。在这些小鼠中，Runx1应选择性地从颅骨和边缘原基的早期间充质中去除。μCT分析显示，Runx1-Cko的骨小梁密度明显低于对照组。此外，10周龄RUNX1-CKO小鼠的骨髓基质细胞培养(BMSCs)显示，RUNX1-CKO小鼠的骨髓基质成骨集落数与总集落形成数(集落形成单位碱性磷酸酶/CFU-成纤维细胞)相比明显减少。综上所述，这些结果提示RUNX1对小鼠的成骨有一定的作用。

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.