Dentin matrix protein 1, a target molecule for Cbfa1 in bone, is a unique bone marker gene
Dentin matrix protein 1, a target molecule for Cbfa1 in bone, is a unique bone marker gene
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DOI：
10.1359/jbmr.2002.17.10.1822
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发表时间：
2002-10-01
影响因子：
6.2
通讯作者：
MacDougall, M
中科院分区：
文献类型：
--
作者：
Feng, JQ;Zhang, JH;MacDougall, M
牙本质基质蛋白1(Dmp1)是一种与牙本质形成高度相关的磷蛋白，据报道也在骨骼中表达。然而，Dmp1在骨骼组织中的作用尚不清楚。为了阐明Dmp1在骨形成中的作用，我们研究了Dmp1在骨和软骨中的表达谱，并检测了Dmp1的表达是否受核心结合因子α(Cbfa1)的调节。对胎鼠颅骨细胞培养的研究表明，Dmp1的表达与体外“骨结节”的形成和矿化密切相关。用原位杂交技术研究了Dmp1在小鼠胚胎发育过程中的时空表达模式，结果表明，Dmp1首先在肥大的软骨细胞中表达，然后在成骨细胞中表达，最后在骨细胞中强烈表达。在发育过程中，Cbfa1和Dmp1在软骨和骨中的表达谱重叠，Cbfa1先于Dmp1。对Cbfa1(-/-)小鼠的Dmp1表达的检测表明，在Cbfa1基因缺失的小鼠发育中的骨骼中不存在Dmp1，而在停滞的牙芽中Dmp1的表达基本上没有变化。瞬时转染研究表明，Dmp1在Cbfa1调控下强制表达，凝胶漂移数据表明在Dmp1近端启动子区域存在功能性骨钙素特异性元件(OSE)-2反应元件。然而，体外启动子研究表明，Cbfa1对Dmp1的调控不是通过Cbfa1与该位点的直接结合介导的，而可能是通过间接机制实现的。这些研究强调Dmp1是成骨细胞分化的唯一标记基因。Dmp1和Cbfa1在发育中的骨骼中密切相关，提示Dmp1可能在骨形成中发挥重要作用。
Dentin matrix protein 1 (Dmp1), a phosphoprotein highly linked to dentin formation, has also been reported to be expressed in the skeleton. However, the role of Dmp1 in skeletal tissues remains unclear. To clarify the role of Dmp1 in bone formation, we characterized the expression profile of Dmp1 in bone and cartilage and examined whether Dmp1 expression was regulated by core-binding factor al (Cbfa1). Studies of fetal rat calvarial (FRC) cell cultures showed that the expression of Dmp1 was associated closely with "bone nodule" formation and mineralization in vitro. In situ hybridization studies were performed to examine the spatial and temporal expression patterns of Dmp1 during development in mouse embryos from 12.5 day postcoitus (dpc) to 8 weeks; postnatal; these studies showed that Dmp1 first appeared in hypertrophic cartilage cells, followed by osteoblasts, and later was expressed strongly in osteocytes. The expression profiles of Cbfa1 and Dmp1 overlapped in both cartilage and bone during development, with Cbfa1 preceding Dmp1. Examination of Dmp1 expression in Cbfa1(-/-) mice revealed that Dmp1 was absent in the developing bones of Cbfa1-null mice, whereas there was essentially no change in Dmp1 expression in the arrested tooth bud. Transient transfection studies showed forced expression of Dmp1 tinder the control of Cbfa1 and gel shift data indicated the presence of a functional osteocalcin-specific element (OSE)-2 response element in the Dmp1 proximal promoter region. However, in vitro promoter studies suggested that regulation of Dmp1 by Cbfa1 was not mediated by direct binding of Cbfa1 to this site and may be through indirect mechanisms. These studies highlight Dmp1 as a unique marker gene for osteoblastic differentiation. The close association of Dmp1 and Cbfa1 in the developing skeleton suggests that Dmp1 may play an important role in bone formation.