Regulatory mechanisms of central nervous system by Runx2

我们之前已经展示了谷氨酸和GABA能信号机制在包括成骨细胞在内的不同骨细胞中的功能表达。Runt相关因子2(Runx2)是成骨细胞分化的主要调节因子，具有促进间充质干细胞向成骨细胞分化的能力，同时我们也证实了Runx2的mRNA和相应蛋白的表达。在这项研究中，我们第一次产生了携带条件Runx2等位基因的小鼠，该等位基因带有外显子4，编码Runt域，两侧有loxP位点。将这些小鼠分别与α1(I)-胶原-Cre或α1(II)-胶原-Cre转基因小鼠杂交，获得成骨细胞或软骨细胞特异性的Runx2缺陷小鼠。在新生α1(II)-Cre；Runx2^FLOX/FLOX小鼠中，矿化损伤仅限于经历软骨内成骨的骨骼区域，包括长骨和椎骨。相反，在突变的胚胎、新生儿和3-6周龄的小鼠中，没有发现明显的骨骼异常，在这些小鼠中，α1(I)-胶原-Cre驱动程序已经缺失了Runx2。这里建立的Runx2等位基因对于研究Runx2在特定细胞中的作用无疑是有用的。

We have previously shown the functional expression of glutamatergic and GABAergic signaling machineries in different osseous cells including osteoblasts. Runt-related factor 2 (Runx2) is the master regulator of osteoblastic differentiation with ability to accelerate differentiation of mesenchymal stem cells into osteoblasts, while we have also demonstrated the expression of mRNA and corresponding protein for Runx2. In this study, we for the first time generated mice carrying a conditional Runx2 allele with exon 4, which encodes the Runt domain, flanked by loxP sites. These mice were crossed with α1(I)-collagen-Cre or α1(II)-collagen-Cre transgenic mice to obtain osteoblast- or chondrocyte-specific Runx2 deficient mice, respectively. In newborn α1(II)-Cre;Runx2^flox/flox mice, mineralization impairment was restricted to skeletal areas undergoing endochondral ossification including long bones and vertebrae. In contrast, no apparent skeletal abnormalities were seen in mutant embryo, newborn, and 3- to 6-week old-mice in which Runx2 had been deleted with the α1(I)-collagen-Cre driver. The Runx2 floxed allele established here is undoubtedly useful for investigating the role of Runx2 in particular cells.