Glycosylation of Dentin Matrix Protein 1 is critical for osteogenesis.
Glycosylation of Dentin Matrix Protein 1 is critical for osteogenesis.
复制标题
牙本质基质蛋白 1 的糖基化对于成骨至关重要。
DOI：
10.1038/srep17518
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发表时间：
2015-12-04
影响因子：
4.6
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Sun Y;Weng Y;Zhang C;Liu Y;Kang C;Liu Z;Jing B;Zhang Q;Wang Z
蛋白多糖在调节成骨过程中起重要作用。牙本质基质蛋白1（Dentin matrix protein 1，DMP 1）是一种高表达的骨细胞外基质蛋白，其调节骨发育和磷酸盐代谢。糖基化后，DMP 1蛋白的N端片段被鉴定为骨基质中的一种新的蛋白聚糖（DMP 1-PG）。体外研究表明，Ser 89是小鼠DMP 1的关键糖基化位点。然而，DMP 1糖基化的具体作用仍不清楚。在本研究中，开发了突变型DMP 1小鼠模型，其中糖基化位点S89被G89取代（S89 G-DMP 1）。S89 G-DMP 1小鼠骨基质中DMP 1糖基化水平下调。与野生型小鼠相比，S89 G-DMP 1小鼠的长骨发生了发育性变化，包括骨重建和矿化速度、骨细胞形态和活性、成骨细胞和破骨细胞的活性。这些结果表明，糖基化的DMP 1是一个关键的翻译后修饰过程中的发展和DMP 1-PG功能作为一个不可缺少的蛋白多糖在骨形成。
Proteoglycans play important roles in regulating osteogenesis. Dentin matrix protein 1 (DMP1) is a highly expressed bone extracellular matrix protein that regulates both bone development and phosphate metabolism. After glycosylation, an N-terminal fragment of DMP1 protein was identified as a new proteoglycan (DMP1-PG) in bone matrix. In vitro investigations showed that Ser89 is the key glycosylation site in mouse DMP1. However, the specific role of DMP1 glycosylation is still not understood. In this study, a mutant DMP1 mouse model was developed in which the glycosylation site S89 was substituted with G89 (S89G-DMP1). The glycosylation level of DMP1 was down-regulated in the bone matrix of S89G-DMP1 mice. Compared with wild type mice, the long bones of S89G-DMP1 mice showed developmental changes, including the speed of bone remodeling and mineralization, the morphology and activities of osteocytes, and activities of both osteoblasts and osteoclasts. These findings indicate that glycosylation of DMP1 is a key posttranslational modification process during development and that DMP1-PG functions as an indispensable proteoglycan in osteogenesis.