Novel proteins of the enamel gene cluster: implications for biomineralization

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Dental enamel is the hardest substance in humans. It consists mainly of hydroxyapatite (HA), a specialized form of calcium phosphate mineral. The crystals of HA in enamel are arranged in a highly ordered fashion, so that enamel does not only have extraordinary hardness, but also flexural strength. The combined mechanical and chemical properties of enamel make it a superior biomaterial that is designed to last a lifetime - if properly formed and cared for - under constant mechanical stress, temperature and pH changes as well as exposure to oral bacteria. The fine structure of enamel reveals four distinct layers: initial, bulk, outer and surface enamel. The structures of these four layers are distinct, but it is not known what determines the transition between them. Although several proteins have been identified and studied in the context of bulk enamel, the mechanisms that lead to surface enamel formation are poorly understood. Surface enamel , however, is the critical interface for the adherence of oral microorganisms, which is the initial step for tooth erosion and decay (e.g. caries). We have previously identified a novel protein, which we have named amelotin (AMTN), in the outer layer of enamel and shown in various mouse models that AMTN is a likely regulator fo this enamel surface structure. In this proposal we suggest experiments to determine if and how AMTN influences the growth and structure of hydroxyapatite crystals, and whether AMTN can help regenerate the enamel surface structure in extracted human teeth. The region in the human genome where the AMTN gene is located contains other enamel genes, but also several uncharacterized genes. The expression of these novel genes will also be studied in this proposal, and relevant gene products will be tested for their ability to modulate enamel biomineralization. This research is expected to improve our understanding of basic biomineralization mechanisms and may lead to the development of novel strategies to protect the tooth surface from decay and erosion. It may also lead to new technologies for the design of novel biomaterials.