Studies on functional roles of crystal-matrix protein interaction in developmental enamel mineralization

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Enamel formation is a complex biomineralization process, which comprises temporo-spatially orchestrated events, e.g., cellular proliferation and differentiation through the sequential epithelial-mesenchymal interactions, secretion of the tissue-specific matrix proteins and construction of their oligomeric molecular structures in the extracellular space, and precipitation/growth and three-dimonsionally oriented alignment of the largest carbonatoapatites in the body through the multiple interactions between organic and inorganic molecules. In comparison with dentinogenesis and osteogenesis, enamel formation is characterized by several unique features : (a) most of the secreted proteins are degraded in situ by multiple proteases and are removed from the tissue, (b) the growth of enamel crystals proceeds gradually through all the developmental stages, and (c) the mineralization process is not intervened by any remodeling of the formed tissue. These unique biominoralization processes are ex … More ecuted, at least in part depending on the tight cellular regulation of mass transport, e.g., transport of common ions (e.g, , Ca^<2+> and phosphate) and impurities (e.g., carbonate) from blood circulation into the extracellular space. In order to investinate the regulatory mechanism of biomineralization, our effort during the current period was focused on development of an experimental precipitation model by modifying a commercially available dialysis chamber. In designing the experimental apparatus, key considerations we took into account are : (a) utilizing a supersaturated solution as prodicted in in situ fluid phase, (b) coating apatite seeds with enamel proteins as found in the secretory enamel, and (c) limiting Ca supply into media surrounding the seed crystals as supposed in situ by previous autoradiographic work. The results obtained support the hypothesis that, under the situation where Ca supply becomes a rate-detormining step in the whole process, (i) the steady state condition with respect to the common ions is achievable in the mineralizing milieu and (ii) the resulting liquid composition depends in a sensitive manner on the presence of regulators for apatite precipitation, namely, enamel proteins and F-. Particularly, in relation to understanding of the pathogenosis of enamel fluorosis, which is now characterized by the delay of tissue maturation caused by excess incorporation of fluoride into the extracellular environment, the current work provided evidence for the effects of fluoride on Ca concentration in the mineralizing milieu. Less