Dentin sialophosphoprotein and dentin matrix protein-1: Two highly phosphorylated proteins in mineralized tissues.

Dentin sialophosphoprotein and dentin matrix protein-1: Two highly phosphorylated proteins in mineralized tissues.
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DOI:
10.1016/j.archoralbio.2012.03.005
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发表时间:
2012-09
影响因子:
3
通讯作者:
Kulkarni, Ashok B.
Kulkarni, Ashok B.
中科院分区:
医学4区
文献类型:
--
作者:
Suzuki, Shigeki;Haruyama, Naoto;Nishimura, Fusanori;Kulkarni, Ashok B.

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牙本质涎磷蛋白(DSPP)和牙本质基质蛋白-1(DMP-1)是高度磷酸化的蛋白质,属于小整合素结合配体N-连接糖蛋白家族,对牙齿和骨骼等硬组织的正常发育是必不可少的。为了了解它们对组织组织的贡献,十多年来,人们使用体内和体外技术对DSPP和DMP-1进行了分析。在这五个兄弟姐妹中,DSPP和DMP-1基因位于彼此相邻的位置,他们的基因和蛋白质结构最相似。在这篇综述中,我们检查了DSPP和DMP-1基因工程小鼠模型的表型,并介绍了对这些表型背后的分子机制的补充体外研究。与DMP-1相比,DSPP对牙本质矿化的影响更为深远。相反,DMP-1通过调节血清成纤维细胞生长因子-23水平显著影响骨矿化和控制血磷水平,而DSPP不表现出任何全身效应。DMP-1激活整合素信号,并内吞到细胞质中,然后转位到细胞核。相反,DSPP只激活整合素依赖的信号转导。因此,现在很清楚,DSPP和DMP-1都有助于硬组织矿化,而且它们影响的组织可能是不同的,这可能是因为它们的表达水平不同。事实上,与DMP-1相比,DSPP对细胞信号转导的功能分析还相对较少。
Dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1) are highly phosphorylated proteins that belong to the family of small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and are essential for proper development of hard tissues such as teeth and bones. In order to understand how they contribute to tissue organization, DSPP and DMP-1 have been analyzed for over a decade using both in vivo and in vitro techniques. Among the five SIBLINGs, the DSPP and DMP-1 genes are located next to each other and their gene and protein structures are most similar. In this review we examine the phenotypes of the genetically engineered mouse models of DSPP and DMP-1 and also introduce complementary in vitro studies into the molecular mechanisms underlying these phenotypes. DSPP affects the mineralization of dentin more profoundly than DMP-1. In contrast, DMP-1 significantly affects bone mineralization and importantly controls serum phosphate levels by regulating serum FGF-23 levels, whereas DSPP does not show any systemic effects. DMP-1 activates integrin signaling and is endocytosed into the cytoplasm whereupon it is translocated to the nucleus. In contrast, DSPP only activates integrin-dependent signaling. Thus it is now clear that both DSPP and DMP-1 contribute to hard tissue mineralization and the tissues affected by each are different presumably as a result of their different expression levels. In fact, in comparison with DMP-1, the functional analysis of cell signaling by DSPP remains relatively unexplored.
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作者:
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