The essential requirement for Runx1 in the development of the sternum
The essential requirement for Runx1 in the development of the sternum
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DOI：
10.1016/j.ydbio.2010.02.005
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发表时间：
2010-04-15
影响因子：
2.7
通讯作者：
Medvinsky, Alexander
中科院分区：
文献类型：
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作者：
Liakhovitskaia, Anna;Lana-Elola, Eva;Medvinsky, Alexander
Runx1在软骨祖细胞和骨祖细胞中高度表达，体外实验表明Runx1在成骨细胞和软骨细胞分化的早期阶段很重要。然而，由于Runx1基因敲除小鼠因造血功能衰竭在胚胎早期死亡，Runx1在骨骼发生中的作用仍不清楚。我们使用Runx1可逆性基因敲除小鼠模型研究了Runx1在骨骼发育中的作用。通过与Tie2 - Cre删除小鼠杂交，Runx1的表达在内皮和造血系统中选择性恢复，但在骨骼中没有恢复。尽管Runx1(Re/Re)胚胎存活至出生且骨骼大体正常，但胸骨和一些颅骨成分的矿化发育明显受阻。与野生型胚胎相比，E17.5的Runx1(Re/Re)胚胎的胸骨显示出高水平的Sox - 9和II型胶原蛋白表达，且缺乏肥大软骨细胞的发育。原位杂交分析表明，与脊椎和长骨不同，野生型胚胎的胸骨表达高水平的Runx1，但不表达骨骼发生的主要调节因子Runx2。因此，尽管Runx1对主要骨骼发育不是必需的，但它在胸骨和一些颅骨成分的发育中确实起着至关重要的作用。(C) 2010爱思唯尔公司。保留所有权利。
Runx1 is highly expressed in chondroprogenitor and osteoprogenitor cells and in vitro experiments suggest that Runx1 is important in the early stages of osteoblast and chondrocyte differentiation. However, because Runx1 knockout mice are early embryonic lethal due to failure of hematopoiesis, the role of Runx1 in skeletogenesis remains unclear. We studied the role of Runx1 in skeletal development using a Runx1 reversible knockout mouse model. By crossing with Tie2-Cre deletor mice, Runx1 expression was selectively rescued in the endothelial and hematopoietic systems but not in the skeleton. Although Runx1(Re/Re) embryos survived until birth and had a generally normal skeleton, the development of mineralization in the sternum and some skull elements was significantly disrupted. In contrast to wild-type embryos, the sternum of E17.5 Runx1(Re/Re) embryos showed high levels of Sox-9 and collagen type II expression and lack of development of hypertrophic chondrocytes. In situ hybridization analysis demonstrated that, in contrast to the vertebrae and long bones, the sternum of wild-type embryos expresses high levels of Runx1, but not Runx2, the master regulator of skeletogenesis. Thus, although Runx1 is not essential for major skeletal development, it does play an essential role in the development of the sternum and some skull elements. (C) 2010 Elsevier Inc. All rights reserved.