Teeth are hierarchically organized structures consisting of ectodermally derived enamel and ectomesenchyntally derived dentin united by the dentino-enamel junction (DEJ). Remarkably, the DEJ robustly unites stiff brittle enamel with flexible tough dentin, because dissimilar materials usually concentrate stresses and delaminate. Enamel provides a hard, wear and acid resistant masticatory surface, whereas dentin absorbs energy and resists fracture. Thus the success of teeth is dependent upon the DEJ. Although much new knowledge on the genetics of tooth formation has become available, knowledge of structure has lagged behind. We propose a series of experiments, using designed perturbations in the commonest proteins in enamel and dentin matrices, amelogenin and type I collagen respectively in transgenic mice, to elucidate the DEJs genetic-structural-functional relationships. We predict that removal of the amelogenin assembly motifs will prevent normal amelogenin self-assembly, producing both bulk enamel defects and as DEJ defects. Using a type I collagen defect mouse we predict that both dentin and DEJ defects will be produced, because not only will enamel form against a defective dentin matrix intaglio, but that collagen may have a direct structural action bridging dentin to enamel at the DES. We predict that the defects will be identifiable using fracture mechanics and imaging techniques. Failure modes of the DEJ will be identified and linked to specific proteins and their genes. Strategies utilized by the DES to avoid catastrophic damage will be characterized. Defined genetic defects will be linked to specific structural outcomes.
Specific aims are: 1) To measure and compare enamel fracture toughness and hardness in three dimensions of normal wild type mice to that of the transgenic amelogenin self assembly defect mice; 2) To measure and compare dentin hardness in normal wild type mice to that of transgenic type I collagen defect mice; 3) To measure and compare DEJ interfacial fracture toughness and DES failure mechanisms in normal wild type mice; with those in transgenic amelogenin self assembly defect mice, and type I collagen defect mice. Ultimately, this work will permit the future development of specific animal models of inherited enamel defects that affect humans; allow better biomimetic interfaces between artificial restorations and dentin to be designed; and lead to an artificial tissue-engineered DEJ.
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