title: CPNE7, a preameloblast-derived factor, regulates odontoblastic differentiation of mesenchymal stem cells.
abstract: Tooth development involves sequential interactions between dental epithelial and mesenchymal cells. Our previous studies demonstrated that preameloblast-conditioned medium (PA-CM) induces the odontogenic differentiation of human dental pulp cells (hDPCs), and the novel protein Cpne7 in PA-CM was suggested as a candidate signaling molecule. In the present study, we investigated biological function and mechanisms of Cpne7 in regulation of odontoblast differentiation. Cpne7 was expressed in preameloblasts and secreted extracellularly during ameloblast differentiation. After secretion, Cpne7 protein was translocated to differentiating odontoblasts. In odontoblasts, Cpne7 promoted odontoblastic markers and the expression of Dspp in vitro. Cpne7 also induced odontoblast differentiation and promoted dentin/pulp-like tissue formation in hDPCs in vivo. Moreover, Cpne7 induced differentiation into odontoblasts of non-dental mesenchymal stem cells in vitro, and promoted formation of dentin-like tissues including the structure of dentinal tubules in vivo. Mechanistically, Cpne7 interacted with Nucleolin and modulated odontoblast differentiation via the control of Dspp expression. These results suggest Cpne7 is a diffusible signaling molecule that is secreted by preameloblasts, and regulates the differentiation of mesenchymal cells of dental or non-dental origin into odontoblasts.
authors.affiliation: Department of Oral Histology-Developmental Biology, School of Dentistry and Dental Research Institute, BK 21, Seoul National University, Seoul 110-749, Republic of Korea.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Oh
authors.affiliation: Department of Oral Histology-Developmental Biology, School of Dentistry and Dental Research Institute, BK 21, Seoul National University, Seoul 110-749, Republic of Korea.
authors.forename: Han-Wool
authors.initials: HW
authors.lastname: Choung
authors.affiliation: Department of Oral Histology-Developmental Biology, School of Dentistry and Dental Research Institute, BK 21, Seoul National University, Seoul 110-749, Republic of Korea.
authors.forename: Hye-Kyung
authors.initials: HK
authors.lastname: Lee
authors.affiliation: Department of Oral Histology-Developmental Biology, School of Dentistry and Dental Research Institute, BK 21, Seoul National University, Seoul 110-749, Republic of Korea.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Oral Histology-Developmental Biology, School of Dentistry and Dental Research Institute, BK 21, Seoul National University, Seoul 110-749, Republic of Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Oral Histology-Developmental Biology, School of Dentistry and Dental Research Institute, BK 21, Seoul National University, Seoul 110-749, Republic of Korea.
authors.forename: Dong-Seol
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea.
authors.forename: Byoung-Moo
authors.initials: BM
authors.lastname: Seo
authors.affiliation: Department of Oral Histology-Developmental Biology, School of Dentistry and Dental Research Institute, BK 21, Seoul National University, Seoul 110-749, Republic of Korea. Electronic address: jcapark@snu.ac.kr.
authors.forename: Joo-Cheol
authors.initials: JC
authors.lastname: Park
mesh_terms: D000565:Ameloblasts / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D003782:Dental Pulp / Q000166:cytology; D003804:Dentin / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D009804:Odontoblasts / Q000166:cytology* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D016601:RNA-Binding Proteins / Q000378:metabolism; D012795:Sialoglycoproteins / Q000378:metabolism; D000097796:Nucleolin; D000099311:Dentin Sialophosphoprotein
chemical_list: D016326:Extracellular Matrix Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D012795:Sialoglycoproteins; D000097796:Nucleolin; D000099311:Dentin Sialophosphoprotein; C400933:CPNE7 protein, human
keywords: Biomineralisation; Dentine; Mesenchymal stem cell; Transplantation