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

Runx1（AML1）编码造血相关转录因子，其突变在人类白血病中经常遇到。因此，为了研究Runx1在骨骼发育中的潜在作用，我们使用aCre-loxP系统（Prx-Cre; Runx1^<fl/fl>: Runx1- cko， fl: floxed等位基因）系统分析了Runx1被去除的小鼠骨骼。在这些小鼠中，runx1应该选择性地从颅间质和缘原基的早期间质中被清除。μCT分析显示，Runx1-cKO的骨小梁骨密度明显低于对照组。此外，10周龄Runx1-cKO小鼠骨髓源性基质细胞培养（BMSCs）显示，与对照小鼠相比，Runx1-cKO小鼠的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）有所减少。综上所述，这些结果表明Runx1有助于小鼠成骨。

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.