Developmental Dynamics of Enamel Formation

牙釉质形成的发育动力学

• 批准号: 7588309
• 负责人: PETROS PAPAGERAKIS
• 金额: $ 19.31万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-05 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7588309
• 关键词: Affect; Ameloblasts; Anthropology; Archaeology; Bicuspid; Biological; Biological Process; Cells; Cervical; Cessation of life; Characteristics; Computer Simulation; Data; Dental; Dental Enamel; Dental crowns; Dentin; Dentinoenamel junction; Development; Developmental Biology; Developmental Process; Disease; Enamel Formation; Event; Evolution; Forensic Dentistry; Foundations; Future; Genes; Genetic; Growth; Horns; Hour; Human; Individual; Knowledge; Malnutrition; Maps; Measurement; Measures; Microscopic; Microtomy; Modeling; Molecular; Morphogenesis; Morphology; Movement; Numerical value; Paleontology; Process; Recording of previous events; Regulation; Relative (related person); Research; Shapes; Side; Signal Transduction; Simulate; Staging; Structure; Surface; Techniques; Testing; Thick; Tissue Engineering; Tooth structure; Vertebrates; base; comparative; computerized; enamel matrix proteins; improved; insight; mathematical model; public health relevance; reconstruction; simulation; three-dimensional modeling

DESCRIPTION (provided by applicant): The morphology of a dental crown is controlled by a strictly regulated spatio-temporal expression of ameloblast specific genes encoding for enamel matrix proteins. Once ameloblasts enter the differentiation stage along the dentino-enamel junction (DEJ) and begin to secrete enamel matrix proteins, they also start moving away from the DEJ and toward the outer enamel surface (OES) whilst forming enamel prisms. Once ameloblasts reach the OES, appositional growth terminates locally and this transition spreads to the cells located farther down the cusp until it reaches the cells at the cervical margin (CM). As the enamel thickens due to appositional growth, it also broadens (as more ameloblasts differentiate and extend the DEJ down the slopes of the crown). This extension eventually slows down and finally stops as the last ring of ameloblasts enter secretory stage, also at the CM. Enamel formation is subjected to rhythmical molecular signals that occur on short (24 hour) periods and give rise to cross-striations, or lines perpendicular to each prism. Another, more marked disturbance, occurs over longer periods (once every 6-10 days depending upon the individual), and induces the formation of striae of Retzius (SR), which are long-period growth markers. Little is known about the mechanisms regulating enamel formation, but careful analysis of short- and long-period growth lines should permit quantification of the critical parameters that determine crown shape during development. We hypothesize that these developmental events are best understood within a conceptual framework that envisions enamel crown shape to be determined by the biological regulation of five parameters: 1) appositional growth rate, 2) duration of appositional growth, 3) extension rate, 4) the duration of ameloblast extension, and 5) spreading rate of appositional termination. We also hypothesize that because a record of enamel formation can be identified by cross- striations and SR lines, obtaining accurate numerical values for the five parameters governing the shape of the ameloblast layer is feasible and might improve our understanding of how enamel forms. Our specific aims are: (1) To measure the distances between enamel growth lines representative of the apposition, extension, and termination processes and to identify landmarks documenting daily enamel formation; and (2) To develop a mathematical model that generates a 3D computerized reconstruction of the crown by accurately simulating dental enamel growth based upon measurements of the growth and developmental parameters that actually determine crown form. This information will fill critical gaps in our knowledge of enamel development, improve understanding pathological enamel formation and may also provide a mathematical foundation for dental tissue engineering. PUBLIC HEALTH RELEVANCE: Teeth form incrementally with characteristic short- and long-period growth markings in enamel. We hypothesize that these markings can be accurately measured using a combination of microscopic techniques. We also believe that the values obtained can be represented mathematically and used to generate a 3D model of enamel formation with the aim of increasing our understanding of development and of diseases affecting enamel.

描述（由申请人提供）：牙冠的形态由严格调节的时空表达，该时空表达编码的搪瓷基质蛋白编码的ameleblast特定基因。一旦成熟的细胞进入Dentino-Enamel结（DEJ）的分化阶段并开始分泌搪瓷基质蛋白，它们也开始从DEJ移开，向外搪瓷表面（OES）移动，同时形成搪瓷棱镜。一旦成熟细胞到达OES，同位生长就会在局部终止，并且该过渡扩散到位于尖端下方的细胞，直到它在宫颈边缘（CM）处到达细胞。随着牙釉质由于同位生长的增长而变厚，它也扩大了（随着越来越多的成成木分化并将DEJ延伸到冠的斜坡上）。最终，随着阿不素细胞的最后一个戒指进入分泌阶段，也最终停止了。牙釉质形成受到短（24小时）时期发生的节奏分子信号，并引起交叉裂纹或垂直于每个棱镜的线。另一个更明显的干扰发生在更长的时间内（每6-10天一次，取决于个体），并诱发了retzius（SR）的形成，后者是长期生长标记物。关于调节搪瓷形成的机制知之甚少，但是对短期和长期生长线的仔细分析应允许量化确定发育过程中冠状形状的关键参数。我们假设最好在一个概念框架内理解这些发育事件，该概念框架设想了牙釉质冠状形状由五个参数的生物学调节确定：1）同伴生长速率，2）申请年生长持续时间，3）扩展率，4）延长速度，4）无素细胞扩展的持续时间，以及5）附属定位终止的扩散率。我们还假设，因为可以通过横纹和SR线识别搪瓷形成的记录，从而获得了五个参数的五个参数的准确数值值，这些参数是可行的，并且可以提高我们对搪瓷形式的理解。我们的具体目的是：（1）衡量代表同名，扩展和终止过程的搪瓷生长线之间的距离，并确定记录每日搪瓷形成的地标； （2）开发一个数学模型，该模型通过基于实际确定冠状形式的生长和发育参数的测量来准确模拟牙齿牙釉质生长，从而生成3D计算机化的牙冠重建。这些信息将填补我们对搪瓷发育知识的关键空白，改善理解病理搪瓷形成，还可能为牙科组织工程提供数学基础。 公共卫生相关性：牙齿逐渐形成牙齿的特征性短期和长期增长标记。我们假设可以使用微观技术的组合来准确测量这些标记。我们还认为，获得的价值可以用数学代表，并用于生成搪瓷形成的3D模型，目的是增加我们对发育和影响搪瓷疾病的理解。