牙本质基质蛋白1及其对骨形成的调控作用

The Roles of Dentin Matrix Protein 1 in Osteogenesis

牙本质基质蛋白1(dentin matrix protein 1,DMP1)是一种高度磷酸化的偏酸性非胶原蛋白,属于小整合素结合配体N端连接糖蛋白(small integrin-binding ligand,N-linked glycoprotein,SIBLINGs)家族.和SIBLINGs家族其它成员一样,DMP1基因定位于人类染色体4q21.除存在于牙组织外,该蛋白还普遍分布于骨组织中.在骨组织与细胞中已发现4种DMP1的主要存在形式,即全长DMP1、57 kD C-DMP1、37 kD N-DMP1、DMP1-PG.它们的分布与功能均不相同,但对骨的正常形成均有重要意义.DMP1的氨基酸序列拥有大量的酸性结构域,携带负电荷,与钙离子有较强的结合能力.它在体外能够促进羟基磷灰石形成,并调控细胞分化,在体内参与硬组织的矿化过程.另外,DMP1的水解过程对其调控矿化的功能十分关键.人体内DMP1基因的突变可导致常染色体隐性低血磷性佝偻病.本文就近几年对DMP1基因结构与调控、蛋白结构与代谢、在骨组织与细胞中的分布及其对骨形成调控作用的研究进展作一综述.

Dentin matrix protein 1（DMP1） is an acidic phosphoprotein of the SIBLING family of noncollagenous proteins（NCPs）.DMP1 is abundant in dentin,and is also distributed in bones as an essential control factor for osteogenesis.Fragmented DMP1 exists within the extracellular matrix of bone,including a 57 kD N-terminal,a 37 kD C-terminal fragment and DMP1-PG.The localization of these DMP1 forms are found in different the bone compartments and cell types suggesting their different roles in osteogenesis.DMP1 contains multiple acidic domains riched in Ser,Glu,and Asp,and many of the Ser reside in the consensus motif of hypothetical phosphorylation sites of casein kinases I and II.The acidic property of DMP1 may allow a high calcium ion-binding capacity that is necessary for mineralization.The proteolytic processing of DMP1,which releases N-DMP1 and C-DMP1,may be important for the formation and mineralization of bones.Experiments indicate a dual biological function for DMP1 both as a transcriptional signal during early differentiation of osteoblasts and as an initiator of mineralization during the terminal differentiation of osteoblasts.Human DMP1 mutations are linked to the condition known as autosomal recessive hypophosphatemic rickets.This review summarizes the late progress in understanding the role of DMP1 in osteogenesis.