MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, University of Edinburgh, Edinburgh EH9 3JQ, UK.
Dev Biol. 2010 Apr 15;340(2):539-46. doi: 10.1016/j.ydbio.2010.02.005. Epub 2010 Feb 10.
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.
Runx1 在软骨祖细胞和成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 敲除小鼠由于造血功能衰竭而在胚胎早期死亡，Runx1 在骨骼发生中的作用仍不清楚。我们使用 Runx1 可逆敲除小鼠模型研究了 Runx1 在骨骼发育中的作用。通过与 Tie2-Cre 缺失小鼠杂交，Runx1 表达在血管内皮细胞和造血系统中被选择性挽救，但在骨骼中没有被挽救。尽管 Runx1(Re/Re) 胚胎存活至出生且具有通常正常的骨骼，但胸骨和一些颅骨元素的矿化发育明显受到破坏。与野生型胚胎相比，E17.5 Runx1(Re/Re) 胚胎的胸骨表现出高水平的 Sox-9 和 II 型胶原表达，并且缺乏肥大软骨细胞的发育。原位杂交分析表明，与椎体和长骨相比，野生型胚胎的胸骨表达高水平的 Runx1，但不表达 Runx2，Runx2 是骨骼发生的主调控因子。因此，尽管 Runx1 对于主要骨骼发育不是必需的，但它确实在胸骨和一些颅骨元素的发育中发挥重要作用。
