Runx2 regulates FGF2-induced Bmp2 expression during cranial bone development
Runx2 regulates FGF2-induced Bmp2 expression during cranial bone development
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DOI：
10.1002/dvdy.20323
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发表时间：
2005-05-01
影响因子：
2.5
通讯作者：
Ryoo, HM
中科院分区：
文献类型：
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作者：
Choi, KY;Kim, HJ;Ryoo, HM
颅骨是由膜内成骨过程形成的，该过程涉及许多信号分子。成纤维细胞生长因子（FGF）信号通路的组成性激活加速成骨细胞分化并导致颅缝过早闭合。骨形态发生蛋白（BMP）信号通路，其涉及下游转录因子Dlx 5和Msx 2，也参与骨形成过程。然而，这两个主要信号级联之间的关系仍然不清楚。我们发现，FGF 2治疗的发展中的骨锋刺激BMP 2基因表达，但BMP 2治疗不能诱导FGF 2的表达。此外，Runx 2基因的破坏完全消除了Bmp 2及其下游基因Dlx 5和Msx 2在发育中的骨原基中的表达，而Fgf 2的表达得以维持。此外，培养的Runx 2-/-细胞表达非常低的Bmp 2基线水平，其通过用Runx 2表达质粒转染而上调。这些水平又通过FGF 2处理显著升高。FGF 2处理还强烈增强了MC 3 T3-E1细胞中的Bmp 2表达，其内源性Runx 2基因是完整的，并且也以低基线水平表达Bmp 2。这些结果表明，Runx 2是一个重要的调解人的表达Bmp 2在响应FGF刺激颅骨发育。(c)2005 Wiley-Liss，Inc.
Calvarial bone is formed by the intramembranous bone-forming process, which involves many signaling molecules. The constitutive activation of the fibroblast growth factor (FGF) signaling pathway accelerates osteoblast differentiation and results in premature cranial suture closure. Bone morphogenetic protein (BMP) signaling pathways, which involve the downstream transcription factors Dlx5 and Msx2, are also involved in the bone-forming processes. However, the relationships between these two main signaling cascades are still unclear. We found that FGF2 treatment of developing bone fronts stimulated Bmp2 gene expression but that BMP2 treatment could not induce Fgf2 expression. Moreover, the disruption of the Runx2 gene completely eliminated the expression of Bmp2 and its downstream genes Dlx5 and Msx2 in the developing primordium of bone, while the expression of Fgf2 was maintained. In addition, cultured Runx2-/- cells expressed very low baseline levels of Bmp2 that were up-regulated by transfection with a Runx2-expressing plasmid. These levels in turn were markedly elevated by FGF2 treatment. FGF2 treatment also strongly enhanced the Bmp2 expression in MC3T3-E1 cells, whose endogenous Runx2 gene is intact and which express Bmp2 at low baseline levels as well. These results indicate that Runx2 is an important mediator of the expression of Bmp2 in response to FGF stimulation in cranial bone development. (c) 2005 Wiley-Liss, Inc.