The purpose of the proposed studies is to improve our understanding of the basic physico-chemical mechanisms of initial enamel mineralization and formation of the dentin-enamel interface. Enamel mineralization starts at the surface of a layer of mineralized dentin, which may play an important role in initial enamel formation. Dentin and enamel are two mineralized tissues with strikingly different mechanical and structural properties that normally perform jointly for tens of years, without failure. Such an outstanding mechanical endurance requires an extraordinarily strong bond between these two tissues. Studies of tooth related genetic disorders and knockout animals demonstrate that the correct formation of the dentin-enamel interface is essential for the proper tooth function. The problem of interface stability is also very important with respect to tissue repair, where often implant failure occurs due to a weak interface between tissues and repair materials. It is likely that interactions between dentin and enamel tissues during initial mineralization play an important role in the proper formation of this critically important interface. We hypothesize that the onset of mineralization at the boundary between enamel and dentin is a highly integrated and specialized process, essential for the proper formation of this mechanically robust interface. We also hypothesize that the mechanism of initial enamel formation at this interface is different from other stages of amelogenesis. We have identified three major factors that distinguish initial enamel formation from later stages of amelogenesis: 1) the presence of dentin mineral at the site of initial enamel formation; 2) the presence of transient mineral phases; and 3) a unique macromolecular composition at the site of initial enamel formation. Thus, we propose a comprehensive study of the formation of the dentin-enamel interface using a variety of in vivo and in vitro approaches to gain a better understanding of basic mechanisms of initial enamel formation. Specifically, we propose in Aim1: To study the interactions between dentin and enamel crystals at the site of initial enamel mineralization, with special emphasis on the epitaxial relationship between dentin and enamel crystals;
in Aim 2 : To study the role of transient amorphous mineral phases in initial stages of enamel formation; and in Aim 3: To study the macromolecular composition at the initial enamel mineralization site with special emphasis on protein-mineral interactions, and to elucidate the possible functions of these macromolecules and supra-molecular assemblies in initial enamel formation using a mechanistic approach, in a series of in vitro mineralization experiments. We expect that the results of this study will improve our knowledge of the basic processes involved in the formation of the dentin-enamel interface that will hopefully lead to the development of new advanced materials and/or procedures for mineralized tissue repair. ? ?
| Duverger, Olivier; Beniash, Elia; Morasso, Maria I (2016) Keratins as components of the enamel organic matrix. Matrix Biol 52-54:260-265 |
| Verdelis, Kostas; Szabo-Rogers, Heather L; Xu, Yang et al. (2016) Accelerated enamel mineralization in Dspp mutant mice. Matrix Biol 52-54:246-259 |
| Sfeir, Charles; Fang, Ping-An; Jayaraman, Thottala et al. (2014) Synthesis of bone-like nanocomposites using multiphosphorylated peptides. Acta Biomater 10:2241-9 |
| Fang, Ping-An; Verdelis, Kostas; Yang, Xu et al. (2014) Ultrastructural organization of dentin in mice lacking dentin sialo-phosphoprotein. Connect Tissue Res 55 Suppl 1:92-6 |
| Lam, Raymond S K; Metzler, Rebecca A; Gilbert, Pupa U P A et al. (2012) Anisotropy of chemical bonds in collagen molecules studied by X-ray absorption near-edge structure (XANES) spectroscopy. ACS Chem Biol 7:476-80 |
| Beniash, Elia; Deshpande, Atul S; Fang, Ping An et al. (2011) Possible role of DMP1 in dentin mineralization. J Struct Biol 174:100-6 |
| Deshpande, Atul Suresh; Fang, Ping-An; Zhang, Xiaoyuan et al. (2011) Primary structure and phosphorylation of dentin matrix protein 1 (DMP1) and dentin phosphophoryn (DPP) uniquely determine their role in biomineralization. Biomacromolecules 12:2933-45 |
| Beniash, Elia (2011) Biominerals--hierarchical nanocomposites: the example of bone. Wiley Interdiscip Rev Nanomed Nanobiotechnol 3:47-69 |
| Fang, Ping-An; Conway, James F; Margolis, Henry C et al. (2011) Hierarchical self-assembly of amelogenin and the regulation of biomineralization at the nanoscale. Proc Natl Acad Sci U S A 108:14097-102 |
| Fang, Ping-An; Margolis, Henry C; Conway, James F et al. (2011) Cryogenic transmission electron microscopy study of amelogenin self-assembly at different pH. Cells Tissues Organs 194:166-70 |
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