title: Globoside accelerates the differentiation of dental epithelial cells into ameloblasts.
abstract: Tooth crown morphogenesis is tightly regulated by the proliferation and differentiation of dental epithelial cells. Globoside (Gb4), a globo-series glycosphingolipid, is highly expressed during embryogenesis as well as organogenesis, including tooth development. We previously reported that Gb4 is dominantly expressed in the neutral lipid fraction of dental epithelial cells. However, because its functional role in tooth development remains unknown, we investigated the involvement of Gb4 in dental epithelial cell differentiation. The expression of Gb4 was detected in ameloblasts of postnatal mouse molars and incisors. A cell culture analysis using HAT-7 cells, a rat-derived dental epithelial cell line, revealed that Gb4 did not promote dental epithelial cell proliferation. Interestingly, exogenous administration of Gb4 enhanced the gene expression of enamel extracellular matrix proteins such as ameloblastin, amelogenin, and enamelin in dental epithelial cells as well as in developing tooth germs. Gb4 also induced the expression of TrkB, one of the key receptors required for ameloblast induction in dental epithelial cells. In contrast, Gb4 downregulated the expression of p75, a receptor for neurotrophins (including neurotrophin-4) and a marker of undifferentiated dental epithelial cells. In addition, we found that exogenous administration of Gb4 to dental epithelial cells stimulated the extracellular signal-regulated kinase and p38 mitogen-activated protein kinase signalling pathways. Furthermore, Gb4 induced the expression of epiprofin and Runx2, the positive regulators for ameloblastin gene transcription. Thus, our results suggest that Gb4 contributes to promoting the differentiation of dental epithelial cells into ameloblasts.
authors: Division of Molecular Pharmacology and Cell Biophysics, Department of Oral Biology, Tohoku University Graduate School of Dentistry, Sendai, Japan.|Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors: Takashi
authors: T
authors: Nakamura
authors: Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors: Yuta
authors: Y
authors: Chiba
authors: Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors: Masahiro
authors: M
authors: Naruse
authors: Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors: Kan
authors: K
authors: Saito
authors: Division of Developmental Biology and Regenerative Medicine, Department of Anatomy, Iwate Medical University, Yahaba, Japan.
authors: Hidemitsu
authors: H
authors: Harada
authors: Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors: Satoshi
authors: S
authors: Fukumoto
mesh_terms: D000565:Ameloblasts / Q000187:drug effects*; D053523:Amelogenin; D000818:Animals; D002454:Cell Differentiation; D003746:Dental Enamel Proteins; D004847:Epithelial Cells; D005915:Globosides / Q000494:pharmacology*; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism
chemical_list: D053523:Amelogenin; D003746:Dental Enamel Proteins; D005915:Globosides; D009414:Nerve Growth Factors; C073922:neurotrophin 4