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

牙釉质的形成是一个复杂的生物矿化过程，包括一系列时空协调的事件，如细胞增殖和分化，通过连续的上皮-间质相互作用，组织特异性基质蛋白的分泌及其在细胞外空间的低聚分子结构的构建。通过有机和无机分子之间的多重相互作用，最大的碳酸盐磷灰石在体内的沉淀/生长和三维定向排列。与牙本质形成和成骨形成相比，牙釉质形成有几个独特的特点：(a)大多数分泌的蛋白质被多种蛋白酶原位降解并从组织中移除，(b)牙釉质晶体的生长在所有发育阶段都是逐渐进行的，(c)矿化过程不受形成组织的任何重塑的干预。这些独特的生物微生物化过程更多地执行，至少部分依赖于质量运输的严格细胞调节，例如，从血液循环到细胞外空间的普通离子（如Ca^<2+ bb0和磷酸盐）和杂质（如碳酸盐）的运输。为了研究生物矿化的调节机制，我们在当前阶段的工作重点是通过修改市售透析室来开发实验性沉淀模型。在设计实验仪器时，我们考虑的关键因素是：(a)使用原位流体相预测的过饱和溶液，(b)用分泌牙釉质中发现的牙釉质蛋白涂覆磷灰石种子，以及(c)限制钙供应到种子晶体周围的介质中，如先前放射自显影工作所假定的原位。所获得的结果支持这样的假设，即在Ca供应成为整个过程中速率决定步骤的情况下，(i)矿化环境中普通离子的稳态条件是可以实现的，（ii）产生的液体成分以敏感的方式依赖于磷灰石沉淀调节因子的存在，即珐琅质蛋白和F-。特别是，对于氟牙釉质中毒的发病机制的理解，目前的特点是由于过量的氟化物进入细胞外环境而导致组织成熟延迟，目前的工作为氟化物对矿化环境中Ca浓度的影响提供了证据。少

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