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）：牙冠的形态由编码釉质基质蛋白的成釉细胞特异性基因的严格调控的时空表达控制。一旦成釉细胞沿着牙本质-釉质交界处（DEJ）进入分化阶段并开始分泌釉质基质蛋白，它们也开始远离DEJ并朝向外釉质表面（OES）移动，同时形成釉质棱柱。一旦成釉细胞到达OES，贴壁生长局部终止，这种过渡扩散到位于更远的牙尖下方的细胞，直到它到达宫颈边缘（CM）的细胞。随着牙釉质因并置生长而变厚，它也会变宽（随着更多的成釉细胞分化并将DEJ沿着牙冠的斜坡延伸）。当最后一环成釉细胞进入分泌期时，这种延伸最终减慢并最终停止，也是在CM处。釉质的形成受到有节奏的分子信号的影响，这些信号在短时间（24小时）内发生，并产生交叉条纹，或垂直于每个棱柱的线。另一种更明显的干扰，发生在较长的时间内（每6-10天一次，取决于个人），并诱导Retzius纹（SR）的形成，这是长期的生长标志。关于调节釉质形成的机制知之甚少，但对短期和长期生长线的仔细分析应该可以量化在发育过程中决定冠状的关键参数。我们假设，这些发展的事件是最好的理解内的概念框架，设想釉质冠的形状，由生物调节的五个参数：1）附着生长速度，2）附着生长的持续时间，3）扩展速率，4）成釉细胞的扩展时间，和5）附着终止的扩展速率。我们还假设，由于釉质形成的记录可以通过横纹和SR线来识别，因此获得控制成釉细胞层形状的五个参数的准确数值是可行的，并且可能提高我们对釉质形成的理解。我们的具体目标是：（1）测量代表附着、延伸和终止过程的釉质生长线之间的距离，并识别记录日常釉质形成的标志;（2）开发一种数学模型，通过基于实际决定牙冠形状的生长和发育参数的测量准确模拟牙釉质生长，生成牙冠的3D计算机重建。这些信息将填补我们对牙釉质发育知识的关键空白，提高对病理性牙釉质形成的理解，也可能为牙齿组织工程提供数学基础。 公共卫生相关性：牙齿逐渐形成，牙釉质中具有特征性的短期和长期生长标记。我们假设这些标记可以使用显微镜技术的组合进行准确测量。我们还认为，获得的值可以用数学表示，并用于生成釉质形成的3D模型，目的是增加我们对发育和影响釉质的疾病的理解。