Saliva-mediated Mechanisms of Post-Eruptive Enamel Mineralization

唾液介导的牙釉质矿化后机制

• 批准号: 9456300
• 负责人: Felicitas B Bidlack
• 金额: $ 29.85万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9456300
• 关键词: Acids; Affect; Ameloblasts; Animal Model; Binding; Biological Models; Biomimetics; Buffers; Chemicals; Child; Cleaved cell; Clinical; Clinical Treatment; Crystallization; Data; Dental Enamel; Dental Pellicle; Dental caries; Development; Diagnosis; Diet; Electron Microscopy; Electrons; Enamel Formation; Environment; Etiology; Excision; Family suidae; Fluorides; Follow-Up Studies; Goals; Growth; Hardness; Helium; Human; Hydroxyapatites; Immunohistochemistry; In Situ; Incisor; Ion Exchange; Ions; Kinetics; Knowledge; Label; Life; Light; Liquid Chromatography; Longevity; Mammals; Measures; Mediating; Methods; Microscopy; Minerals; Modeling; Oral cavity; Outcome Study; Peptide Hydrolases; Peptides; Phase; Predisposition; Preventive measure; Process; Property; Proteins; Proteomics; Public Health; Research; Residual state; Resistance; Resolution; Risk; Role; Saliva; Salivary; Salvelinus; Sampling; Shapes; Structure; Study models; Surface; Testing; Thick; Time; Tooth structure; Vision; Weight; Width; base; calcium phosphate; clinically relevant; density; enamel matrix proteins; follow-up; high resolution imaging; improved; innovation; insight; mechanical properties; mineralization; novel; novel strategies; permanent tooth; prevent; protein B; remineralization; repaired; saliva composition; saliva diagnostic; saliva mediated; tandem mass spectrometry; treatment strategy

Enamel hypomineralization, specifically molar-incisor hypomineralization (MIH), is diagnosed in the permanent dentition of up to 40% of children worldwide, and increases the risk of caries, attrition and reduced durability of fillings. A critical barrier to improving treatment of enamel hypomineralization is the gap in understanding how to amplify the processes of crystal growth and posteruptive enamel maturation. The goal of this project is to take advantage of the porcine model to determine how and how fast pig enamel acquires the hardness to last a lifespan although at eruption it has a mineral density similar to hypomineralized human enamel. Our working hypothesis is that during enamel maturation, mineral content, hardness, and acid resistance increase over time, whereas organic matrix content decreases. The objective of this proposal is to elucidate the mechanisms of naturally occurring posteruptive enamel mineralization in the porcine model system. Our central hypotheses are that 1) pig enamel erupts hypomineralized into the oral cavity with retained organic matrix that arrests crystal growth and results in incomplete mineralization; and 2) after eruption, whole saliva and the dental pellicle forming the interface with the enamel surface mediate the controlled removal of residual organic matrix and ion exchange to effectively continue the maturation process. Because fluoride treatments cannot remove the retained organic matrix that causes enamel softness, the rationale for the proposed studies is that determining how posteruptive mineralization can occur in pig teeth at a much faster rate than in human teeth will allow us to develop biomimetic approaches for enamel repair of MIH-affected human teeth. A follow-up (R01) study will then focus on strategies to improve enamel properties, specifically hardness and chemical resistance, to achieve a rate that is clinically meaningful. To attain these goals, we will test our central hypotheses in two Specific Aims. 1. Elucidate the kinetics of posteruptive enamel maturation in pig teeth by characterizing and quantifying changes in mineral and organic phases of both deciduous and permanent pig enamel at three-month intervals. 2. Characterize the composition of pig whole saliva and dental pellicle to determine if saliva/pellicle constituents facilitate continued mineralization in the absence of ameloblasts. Our results will increase knowledge of the mechanisms of enamel maturation, provide new insights on posteruptive enamel mineralization, and open a new perspective on treatment options. This is significant because retained organic matrix arrests crystal growth and maturation resulting in soft, hypomineralized enamel, which is more susceptible to caries and attrition, and to compromised bonding and durability of fillings. The proposed research is innovative because it 1) applies our unique expertise and research set-up to integrate the porcine model with novel analytical approaches to study the kinetics of enamel maturation and 2) challenges current paradigms that posteruptive enamel mineralization is a very gradual process with low efficiency and that enamel matrix proteases, rather than saliva constituents, facilitate the removal of enamel matrix proteins.

在永久性中诊断出搪瓷低矿化，特别是摩尔菌度低矿化（MIH） 全球多达40％的儿童的牙齿牙列增加了龋齿，流失和降低的耐用性的风险 填充物。改善牙釉质低矿化治疗的关键障碍是理解如何 放大晶体生长和后牙釉质成熟的过程。这个项目的目标是 利用猪模型来确定猪搪瓷如何获得持久的硬度的快速 寿命虽然在喷发时具有类似于低矿物化牙釉质的矿物质密度。我们的工作 假设是，在搪瓷成熟期间，矿物质含量，硬度和耐酸性在 时间，而有机基质含量降低。该提议的目的是阐明机制 猪模型系统中天然发生的后搪瓷矿化。我们的中心假设 是1）用保留的有机基质爆发到口腔中的猪搪瓷爆发到口腔中 晶体生长并导致矿化不完全； 2）喷发后，整个唾液和牙齿 与搪瓷表面形成界面的细胞介导残留有机基质的受控去除 和离子交换以有效地继续成熟过程。因为氟化物治疗无法消除 导致搪瓷柔软性的保留有机基质，拟议的研究的基本原理是 确定猪牙齿中的后矿化如何以比人牙齿快得多的速度发生 将使我们能够开发出仿生方法来修复受MIH影响的人牙齿的修复。跟进 （R01）然后研究将重点放在改善牙釉质特性的策略上，特别是硬度和化学 阻力，以达到临床上有意义的速率。为了实现这些目标，我们将测试我们的中心 假设有两个具体目标。 1。通过 表征和量化落叶和永久性猪的矿物和有机阶段的变化 搪瓷以三个月的间隔。 2。将猪全唾液和牙齿的组成表征 确定在没有成成木的情况下，唾液/颗粒成分是否促进持续矿化。我们的 结果将增加对搪瓷成熟机制的了解，提供有关后爆的新见解 搪瓷矿化，并为治疗方案开辟新的观点。这很重要，因为保留 有机基质会阻止晶体生长和成熟，导致柔软的低矿化搪瓷，这更多 容易受到龋齿和损耗的影响，并损害了填充物的粘结和耐用性。提议 研究具有创新性，因为它1）应用我们独特的专业知识和研究设置来整合猪 具有新的分析方法的模型来研究搪瓷成熟的动力学和2）挑战当前 后爆发搪瓷矿化是一个非常渐进的过程，效率低，并且 搪瓷基质蛋白酶而不是唾液成分，有助于去除牙釉质基质蛋白。