title: Odontogenic differentiation of human dental pulp stem cells induced by preameloblast-derived factors.
abstract: The differentiation of odontoblasts is initiated by the organization of differentiating ameloblasts during tooth formation. However, the exact roles of ameloblast-derived factors in odontoblast differentiation have not yet been characterized. We investigated the effects of preameloblast-conditioned medium (PA-CM) on the odontogenic differentiation of human dental pulp stem cells (hDPSCs) in vitro and in vivo. Furthermore, we analyzed the PA-CM by liquid chromatography-mass spectrometry to identify novel factors that facilitate odontoblast differentiation. In the co-culture of MDPC-23 cells or hDPSCs with mouse apical bud cells (ABCs), ABCs promoted differentiation of odontoblastic MDPC-23 cells and facilitated odontoblast differentiation of hDPSCs. PA-CM, CM from ABCs after 3 days culture, was most effective in increasing the dentin sialophosphoprotein promoter activity of odontoblastic MDPC-23 cells. When PA-CM-treated hDPSCs were transplanted into immunocompromised mice, they generated pulp-like structures lined with human odontoblast-like cells showing typical odontoblast processes. However, during recombinant human bone morphogenenetic protein 2-treated hDPSCs transplantation, some of the cells were entrapped in mineralized matrix possessing osteocyte characteristics. After proteomic analyses, we identified 113 types of proteins in PA-CM, of which we characterized 23. The results show that preameloblast-derived factors induce the odontogenic differentiation of hDPSCs and promote dentin formation.
authors.affiliation: Department of Oral Histology-Developmental Biology & Dental Research Institute, BK21 Project, School of Dentistry, Seoul National University, 28 Yeongun-dong, Chongro-gu, Seoul 110-749, Republic of Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Dong-Seol
authors.initials: DS
authors.lastname: Lee
authors.forename: Han-Wool
authors.initials: HW
authors.lastname: Choung
authors.forename: Won-Jun
authors.initials: WJ
authors.lastname: Shon
authors.forename: Byoung-Moo
authors.initials: BM
authors.lastname: Seo
authors.forename: Eun-Hyang
authors.initials: EH
authors.lastname: Lee
authors.forename: Je-Yoel
authors.initials: JY
authors.lastname: Cho
authors.forename: Joo-Cheol
authors.initials: JC
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000565:Ameloblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D003782:Dental Pulp / Q000166:cytology*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D058574:Integrin-Binding Sialoprotein / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009804:Odontoblasts / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D009805:Odontogenesis / Q000187:drug effects* / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D055815:Young Adult; D000099311:Dentin Sialophosphoprotein
chemical_list: D017077:Culture Media, Conditioned; D016326:Extracellular Matrix Proteins; D058574:Integrin-Binding Sialoprotein; D008565:Membrane Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein