Roles of DMP1 Processing in Osteogenesis, Dentinogenesis and Chondrogenesis
Roles of DMP1 Processing in Osteogenesis, Dentinogenesis and Chondrogenesis
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DOI：
10.1159/000324672
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发表时间：
2011-01-01
影响因子：
2.7
通讯作者：
Qin, Chunlin
中科院分区：
文献类型：
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作者：
Sun, Yao;Chen, Li;Qin, Chunlin
牙本质基质蛋白1（Dentin matrix protein 1，DMP 1）是一种酸性蛋白，在骨形成和牙本质形成中起关键作用。蛋白质化学研究表明，DMP 1主要存在于骨和牙本质的细胞外基质中作为加工的NH（2）-和COOH-末端片段。我们早期的工作表明，在体外用Ala 213取代Asp 213（切割位点的残基）阻断了小鼠DMP 1的加工。最近，我们产生了表达这种突变体DMP 1的转基因小鼠（命名为“D213 A-DMP 1”）。通过将这些转基因小鼠与Dmp 1敲除（Dmp 1-KO）小鼠杂交，我们获得了在Dmp 1缺失背景下表达D213 A-DMP 1转基因的小鼠（命名为“Dmp 1-KO/D213 A-Tg”小鼠）。在这项研究中，我们分析了Dmp 1-KO/D213 A-Tg小鼠的长骨，下颌骨，牙本质和软骨与野生型，Dmp 1-KO和表达正常DMP 1转基因的Dmp 1-KO小鼠（Dmp 1-KO/normal-Tg）进行比较。我们的结果表明，D213 A-DMP 1在Dmp 1-KO/D213 A-Tg小鼠的牙本质基质中几乎没有被切割，并且D213 A-DMP 1的表达未能挽救Dmp 1缺失小鼠的发育缺陷。有趣的是，在DMP 1-KO/D213 A-Tg小鼠中观察到增大的生长板和髁突软骨，表明DMP 1的全长形式在软骨形成中的潜在作用。版权所有（C）2011 S. Karger AG，巴塞尔
Dentin matrix protein 1 (DMP1) is an acidic protein that plays critical roles in osteogenesis and dentinogenesis. Protein chemistry studies have demonstrated that DMP1 primarily exists as processed NH(2)- and COOH-terminal fragments in the extracellular matrix of bone and dentin. Our earlier work showed that the substitution of Asp 213 (a residue at a cleavage site) by Ala 213 blocks the processing of mouse DMP1 in vitro. Recently, we generated transgenic mice expressing this mutant DMP1 (designated 'D213A-DMP1'). By crossbreeding these transgenic mice with Dmp1-knockout (Dmp1-KO) mice, we obtained mice expressing the D213A-DMP1 transgene in the Dmp1-null background (named 'Dmp1-KO/D213A-Tg' mice). In this study, we analyzed the long bone, mandible, dentin, and cartilage of Dmp1-KO/D213A-Tg mice in comparison with wild-type, Dmp1-KO, and Dmp1-KO mice expressing the normal DMP1 transgene (Dmp1-KO/normal-Tg). Our results showed that D213A-DMP1 was barely cleaved in the dentin matrix of Dmp1-KO/D213A-Tg mice and the expression of D213A-DMP1 failed to rescue the developmental defects in Dmp1-null mice. Interestingly, enlarged growth plates and condylar cartilages were observed in Dmp1-KO/D213A-Tg mice, indicating a potential role of the full-length form of DMP1 in chondrogenesis. Copyright (C) 2011 S. Karger AG, Basel