Role of epithelial-stem cell interactions during dental cell differentiation.
Epithelial-mesenchymal interactions regulate the growth and morphogenesis of ectodermal organs such as teeth. Dental pulp stem cells (DPSCs) are a part of dental mesenchyme, derived from the cranial neural crest, and differentiate into dentin forming odontoblasts. However, the interactions between DPSCs and epithelium have not been clearly elucidated. In this study, we established a mouse dental pulp stem cell line (SP) comprised of enriched side population cells that displayed a multipotent capacity to differentiate into odontogenic, osteogenic, adipogenic, and neurogenic cells. We also analyzed the interactions between SP cells and cells from the rat dental epithelial SF2 line. When cultured with SF2 cells, SP cells differentiated into odontoblasts that expressed dentin sialophosphoprotein. This differentiation was regulated by BMP2 and BMP4, and inhibited by the BMP antagonist Noggin. We also found that mouse iPS cells cultured with mitomycin C-treated SF2-24 cells displayed an epithelial cell-like morphology. Those cells expressed the epithelial cell markers p63 and cytokeratin-14, and the ameloblast markers ameloblastin and enamelin, whereas they did not express the endodermal cell marker Gata6 or mesodermal cell marker brachyury. This is the first report of differentiation of iPS cells into ameloblasts via interactions with dental epithelium. Co-culturing with dental epithelial cells appears to induce stem cell differentiation that favors an odontogenic cell fate, which may be a useful approach for tooth bioengineering strategies.
Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.
Makiko
M
Arakaki
Laboratory of Cell and Developmental Biology, NIDCR, National Institutes of Health, Bethesda, Maryland 20892.
Masaki
M
Ishikawa
Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.
Takashi
T
Nakamura
Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.
Tsutomu
T
Iwamoto
Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.
Aya
A
Yamada
Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.
Emiko
E
Fukumoto
Faculty of Industrial Science and Technology, Tokyo University of Science, Chiba 278-8510, Japan, and.
Masahiro
M
Saito
Department of Oral Anatomy II, Iwate Medical College School of Dentistry, Morioka 020-8505, Japan.
Keishi
K
Otsu
Department of Oral Anatomy II, Iwate Medical College School of Dentistry, Morioka 020-8505, Japan.
Hidemitsu
H
Harada
Laboratory of Cell and Developmental Biology, NIDCR, National Institutes of Health, Bethesda, Maryland 20892.
Yoshihiko
Y
Yamada
Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan,. Electronic address: fukumoto@dent.tohoku.ac.jp.
Satoshi
S
Fukumoto
D000818:Animals; D000831:Animals, Newborn; D000943:Antigens, Differentiation / Q000096:biosynthesis; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D018920:Coculture Techniques; D003782:Dental Pulp / Q000166:cytology / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D039902:Multipotent Stem Cells / Q000166:cytology / Q000502:physiology*; D009804:Odontoblasts / Q000166:cytology / Q000502:physiology*; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
D000943:Antigens, Differentiation; C525719:Bmp2 protein, mouse; C525720:Bmp2 protein, rat; C525810:Bmp4 protein, mouse; C525811:Bmp4 protein, rat; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4