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.

牙釉质矿化不足，特别是臼齿-切牙矿化不足（MIH），诊断为永久性 全世界高达40%的儿童的牙齿，并增加龋齿，磨损和耐久性降低的风险。 填充物。改善釉质矿化不足治疗的一个关键障碍是在理解如何改善釉质矿化不足方面存在差距。 以放大晶体生长和发育后釉质成熟的过程。该项目的目标是 利用猪模型来确定猪牙釉质如何以及多快获得硬度以持续 虽然在喷发时，它的矿物质密度类似于矿化不足的人类釉质。我们的工作 有一种假说认为，在釉质成熟过程中，矿物质含量、硬度和抗酸性增加， 时间，而有机基质含量降低。本提案的目的是阐明 在猪模型系统中自然发生的牙釉质矿化。我们的核心假设 1）猪牙釉质喷发低矿化进入口腔，保留有机基质， 晶体生长并导致不完全矿化;和2）萌出后，整个唾液和牙齿 与釉质表面形成界面的薄膜介导残留有机基质的受控去除 和离子交换以有效地继续熟化过程。因为氟化物治疗不能去除 残留的有机基质导致釉质柔软，拟议研究的基本原理是， 确定猪牙齿中的牙萌后矿化如何以比人类牙齿快得多的速度发生 将使我们能够开发仿生方法来修复受MIH影响的人类牙齿的釉质。的后续行动 (R01)然后，研究将集中在改善釉质性能的策略上，特别是硬度和化学性质。 阻力，以达到具有临床意义的速率。为了实现这些目标，我们将测试我们的中央 两个具体目标的假设。1.猪牙釉质发育后釉质成熟的动力学研究 对乳鸽和长白猪的矿物和有机相的变化进行表征和量化 每三个月检查一次牙釉质。2.猪全唾液和牙膜的组成特征， 确定唾液/表膜成分是否在成釉细胞不存在的情况下促进持续矿化。我们 结果将增加对釉质成熟机制的认识， 釉质矿化，并打开一个新的角度对治疗方案。这一点很重要，因为保留 有机基质阻止晶体生长和成熟，导致柔软的低矿化牙釉质， 易受龋齿和磨损的影响，以及易受填充物的粘结和耐久性的影响。拟议 研究是创新的，因为它1）应用我们独特的专业知识和研究设置，以整合猪 模型与新的分析方法来研究釉质成熟的动力学和2）挑战电流 典型的例子是，术后釉质矿化是一个非常缓慢的过程，效率很低， 釉质基质蛋白酶而不是唾液成分促进釉质基质蛋白的去除。