title: Distribution of the amelogenin protein in developing, injured and carious human teeth.
abstract: Amelogenin is the major enamel matrix protein with key roles in amelogenesis. Although for many decades amelogenin was considered to be exclusively expressed by ameloblasts, more recent studies have shown that amelogenin is also expressed in other dental and no-dental cells. However, amelogenin expression in human tissues remains unclear. Here, we show that amelogenin protein is not only expressed during human embryonic development but also in pathological conditions such as carious lesions and injuries after dental cavity preparation. In developing embryonic teeth, amelogenin stage-specific expression is found in all dental epithelia cell populations but with different intensities. In the different layers of enamel matrix, waves of positive vs. negative immunostaining for amelogenin are detected suggesting that the secretion of amelogenin protein is orchestrated by a biological clock. Amelogenin is also expressed transiently in differentiating odontoblasts during predentin formation, but was absent in mature functional odontoblasts. In intact adult teeth, amelogenin was not present in dental pulp, odontoblasts, and dentin. However, in injured and carious adult human teeth amelogenin is strongly re-expressed in newly differentiated odontoblasts and is distributed in the dentinal tubuli under the lesion site. In an in vitro culture system, amelogenin is expressed preferentially in human dental pulp cells that start differentiating into odontoblast-like cells and form mineralization nodules. These data suggest that amelogenin plays important roles not only during cytodifferentiation, but also during tooth repair processes in humans.
authors.affiliation: Orofacial Development and Regeneration Unit, Faculty of Medicine, Institute of Oral Biology, ZZM, University of Zurich Zurich, Switzerland.
authors.forename: Thimios A
authors.initials: TA
authors.lastname: Mitsiadis
authors.affiliation: Orofacial Development and Regeneration Unit, Faculty of Medicine, Institute of Oral Biology, ZZM, University of Zurich Zurich, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Filatova
authors.affiliation: Dipartimento di Medicina Sperimentale, Sezione di Biotecnologie, Istologia Medica e Biologia Molecolare, Seconda Università Degli Studi di Napoli Napoli, Italy.
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Papaccio
authors.affiliation: INSERM UMR-S 1124, Biomédicale des Saints Pères, University Paris Descartes Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Goldberg
authors.affiliation: CNRS, Institut des Sciences du Mouvement UMR 7287, Aix-Marseille Université Marseille, France.
authors.forename: Imad
authors.initials: I
authors.lastname: About
authors.affiliation: Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan Ann Arbor, USA ; Center for Organogenesis, School of Medicine, University of Michigan Ann Arbor, USA ; Center for Computational Medicine and Bioinformatics, School of Medicine, University of Michigan Ann Arbor, USA.
authors.forename: Petros
authors.initials: P
authors.lastname: Papagerakis
keywords: ameloblasts; amelogenin; carious; dental injury; dental pulp; enamel; odontoblast; tooth