title: Differentiation of odontoblasts is negatively regulated by MEPE via its C-terminal fragment.
abstract: 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.
authors.affiliation: Department of Operative Dentistry and Endodontics, School of Stomatology, Fourth Military Medical University, No. 145, Changle West Road, Xian 710032, China.
authors.forename: Hanguo
authors.initials: H
authors.lastname: Wang
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kawashima
authors.forename: Takanori
authors.initials: T
authors.lastname: Iwata
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Satomi
authors.initials: S
authors.lastname: Takahashi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Hideaki
authors.initials: H
authors.lastname: Suda
mesh_terms: D000818:Animals; D002113:Calcification, Physiologic; D002454:Cell Differentiation; D002460:Cell Line; D003810:Dentinogenesis; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009804:Odontoblasts / Q000166:cytology* / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C518716:Mepe protein, mouse; D010750:Phosphoproteins