Department of Operative Dentistry and Endodontics, School of Stomatology, Fourth Military Medical University, No. 145, Changle West Road, Xian 710032, China.
Biochem Biophys Res Commun. 2010 Jul 30;398(3):406-12. doi: 10.1016/j.bbrc.2010.06.085. Epub 2010 Jun 23.
Matrix extracellular phosphoglycoprotein (MEPE) is an extracellular matrix protein that is mainly expressed in mineralizing tissues, including the dental pulp. The purposes of this study were to clarify the localization of MEPE in the tooth germ and to investigate the roles of MEPE in the differentiation of odontoblasts. The immunohistochemical staining in the tooth germ of the upper first molars of male Wistar rats (postnatal day 3) revealed that MEPE was mainly localized in odontoblasts during dentinogenesis. Stable MEPE-overexpressing and MEPE-knockdown cell lines, which were established in odontoblast-lineage cells (OLCs), showed lower and higher differentiation capabilities, respectively. Eukaryotic proteins of the N-terminal fragment of MEPE produced in HEK cells had no effect on the differentiation of OLCs, whereas the C-terminal fragment containing an RGD sequence inhibited their differentiation. These results indicated that the C-terminal fragment of MEPE containing an RGD sequence, cleaved in odontoblasts, appeared to be the active form of MEPE, which may play important roles in dentinogenesis and pulpal homeostasis by keeping the odontoblasts in immature condition.
基质细胞外磷蛋白(MEPE)是一种主要在矿化组织中表达的细胞外基质蛋白,包括牙髓。本研究旨在阐明 MEPE 在牙胚中的定位,并研究 MEPE 在成牙本质细胞分化中的作用。对雄性 Wistar 大鼠(出生后第 3 天)上颌第一磨牙牙胚的免疫组织化学染色显示,MEPE 在牙本质形成过程中主要定位于成牙本质细胞中。在成牙本质细胞系(OLC)中建立的稳定过表达 MEPE 和敲低 MEPE 的细胞系分别表现出较低和较高的分化能力。真核细胞表达的 MEPE N 端片段蛋白对 OLC 的分化没有影响,而含有 RGD 序列的 C 端片段则抑制其分化。这些结果表明,在成牙本质细胞中切割的含有 RGD 序列的 MEPE C 端片段可能是 MEPE 的活性形式,通过使成牙本质细胞保持未成熟状态,在牙本质发生和牙髓稳态中发挥重要作用。