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.

牙釉质低矿化，特别是磨牙-切牙低矿化（MIH），在恒牙中诊断出来。 全球多达 40% 的儿童患有牙列问题，并增加了龋齿、磨损和牙齿耐用性降低的风险 填充物。改善牙釉质矿化不足治疗的一个关键障碍是对如何治疗牙釉质的认识存在差距。 放大晶体生长和牙釉质后成熟的过程。该项目的目标是 利用猪模型来确定猪牙釉质获得持续硬度的方式和速度 尽管在萌发时它的矿物质密度与矿化不足的人类牙釉质相似，但它的寿命很长。我们的工作 假设是，在牙釉质成熟过程中，矿物质含量、硬度和耐酸性随着时间的推移而增加 时间延长，而有机基质含量降低。该提案的目的是阐明机制 猪模型系统中自然发生的后牙釉质矿化。我们的中心假设 是 1) 猪牙釉质在口腔中矿化不足，并保留了阻止其生长的有机基质 晶体生长并导致不完全矿化； 2) 萌出后，全部唾液和牙齿 与牙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成熟过程。因为氟化物处理不能去除 保留的有机基质导致牙釉质柔软，所提出研究的基本原理是 确定猪牙齿中的后期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 影响的人类牙齿的牙釉质。后续行动 (R01) 研究将重点关注改善牙釉质性能的策略，特别是硬度和化学性能 耐药性，以达到有临床意义的速率。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. 通过以下方法阐明猪牙的牙釉质成熟动力学： 表征和量化乳猪和恒猪的矿物质和有机相的变化 每三个月进行一次牙釉质检查。 2. 表征猪全唾液和牙膜的成分 确定在没有成釉细胞的情况下唾液/表膜成分是否促进持续矿化。我们的 结果将增加对牙釉质成熟机制的了解，为牙釉质成熟提供新的见解 牙釉质矿化，并为治疗方案开辟新的视角。这很重要，因为保留了 有机基质阻止晶体生长和成熟，从而产生柔软、矿化程度低的牙釉质，这更有效 容易出现龋齿和磨损，并且填充物的粘合性和耐久性会受到影响。拟议的 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机构来整合猪 模型采用新颖的分析方法来研究牙釉质成熟的动力学，2）挑战当前 认为后牙釉质矿化是一个非常渐进的过程，效率低，并且 牙釉质基质蛋白酶，而不是唾液成分，有助于去除牙釉质基质蛋白。