title: Glycosphingolipids regulate ameloblastin expression in dental epithelial cells.
abstract: Neurotrophin 4 (NT-4) and its receptors regulate the differentiation of ameloblasts in tooth development. Gangliosides, sialic acids that contain glycosphingolipids (GSLs), are involved in a variety of membrane-associated cell physiological functions such as ligand-receptor signal transmission. However, the expression patterns and functions of GSLs during tooth development remain unclear. In this study, we identified strong expressions of GM3 and LacCer in dental epithelium, which give rise to differentiation into enamel-secreting ameloblasts. Exogenous GM3 and LacCer in dental epithelial cells induced the expression of ameloblastin (Ambn), while it was also interesting that GM3 synergistically exerted enhancement of NT-4-mediated Ambn expression. In addition, consistently exogenous GM3 and LacCer in dental epithelial cells induced distinct activation of extracellular signal-regulated kinase 1/2 (ERK1/2), an event upstream of the expression of Ambn. Furthermore, depletion of GSLs from dental epithelial cells by D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) inhibited Ambn expression as well as phosphorylation of ERK1/2. In contrast, exogenous addition of GM3 or LacCer rescued the phosphorylation of ERK1/2 repressed by pre-treatment with D-PDMP. Taken together, these results suggest that GM3 and LacCer are essential for NT-4-mediated Ambn expression, and contribute to dental epithelial cell differentiation into ameloblasts.
authors: Department of Pediatric Dentistry, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. taka@dent.tohoku.ac.jp
authors: Y
authors: Y
authors: Kamasaki
authors: T
authors: T
authors: Nakamura
authors: K
authors: K
authors: Yoshizaki
authors: T
authors: T
authors: Iwamoto
authors: A
authors: A
authors: Yamada
authors: E
authors: E
authors: Fukumoto
authors: Y
authors: Y
authors: Maruya
authors: K
authors: K
authors: Iwabuchi
authors: K
authors: K
authors: Furukawa
authors: T
authors: T
authors: Fujiwara
authors: S
authors: S
authors: Fukumoto
mesh_terms: D000565:Ameloblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000566:Amelogenesis / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D002454:Cell Differentiation; D002460:Cell Line; D003746:Dental Enamel Proteins / Q000096:biosynthesis* / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005679:G(M3) Ganglioside / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D006028:Glycosphingolipids / Q000096:biosynthesis / Q000502:physiology*; D007790:Lactosylceramides / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009414:Nerve Growth Factors / Q000502:physiology; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction
chemical_list: C098519:Ambn protein, rat; D015703:Antigens, CD; D003746:Dental Enamel Proteins; D005679:G(M3) Ganglioside; D006028:Glycosphingolipids; D007790:Lactosylceramides; D009414:Nerve Growth Factors; C009744:CDw17 antigen; D019950:Mitogen-Activated Protein Kinase 1; C073922:neurotrophin 4