Tooth Movement derived by PDL Cellular Manipulations

PDL 细胞操作衍生的牙齿移动

• 批准号: 9134121
• 负责人: Gili Rina Naveh
• 金额: $ 12.8万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9134121
• 关键词: Address; Affect; Area; Award; Biomedical Engineering; Blood Vessels; Bone remodeling; Boston; Clinical; Collagen; Collagen Fiber; Collagen Type I; Complex; Custom; Data; Dental; Dental Schools; Development; Discipline; Disease; Elements; Environment; Fiber; Gene Expression; Generations; Health; Image; In Situ Hybridization; In Vitro; Investigation; Medical; Medicine; Mentors; Methods; Modeling; Modification; Molar tooth; Mouse Strains; Mus; Orthodontic; Orthodontics; Periodontal Ligament; Phase; Photons; Population; Positioning Attribute; Rattus; Reaction; Research; Resolution; Role; Signal Pathway; Structure; Testing; Three-Dimensional Imaging; Time; Tissues; Tooth Movement; Tooth structure; Torsion; Training; Training Programs; Universities; Work; base; bone; experience; extracellular; imaging modality; medical specialties; microCT; multipotent cell; novel; novel strategies; research study; three dimensional structure; tool

 DESCRIPTION (provided by applicant): Tooth movement derived by PDL Cellular Manipulations The ability of teeth to move is essential for their adaptation to the constantly changing environment and therefore for their survival. The periodontal ligament (PDL) has a central role in controlling this tooth movement. However, despite the fundamental role of the PDL, the functional mechanisms and the 3D structure of this remarkable tissue are not fully understood. The proposed study is aimed at elucidating the structure-function basis of the PDL and by doing so to generate a new clinical method for controlled tooth movement. Loads change the fibrous distribution inside the PDL in order to enable certain functions. For instance, orthodontic loads cause changes in PDL fiber structure and trigger a cascade of bone remodeling that eventually leads to a change in the position of the tooth. It was recently shown that the PDL is not uniform in its structure and function even under normal functional loads; in other words, tooth function controls the structure of the PDL. The hypothesis of this proposed project is that intentional modifications in the PDL structure will trigger changes in the surrounding bone and eventually functional tooth changes. This hypothesis will be addressed in four complementary specific aims. The mentored phase (K99) will be conducted with Dr. Bjorn Olsen as mentor and Dr. Leslie Will as a co-mentor, at Harvard School of Dental Medicine and at Boston University School of Dental Medicine. The experiments in this phase are anticipated to establish a 3D characterization of the collagen networks and the cellular populations of the mouse molar tooth PDL. To do so, we will utilize an arsenal of 3D imaging methods, we will use a unique custom-made apparatus inside a microCT as well as 2 photon and 2nd harmonic-generation imaging. For high resolution structural analysis we will also employ STORM and AirSEM methods. We will cross different genetically modified mouse strains to investigate the cellular populations in the PDL and we will take advantage of in-situ hybridization to investigate gene expression levels as well as signaling pathways. Crossing disciplines, bioengineering tools will be used for in- vitro investigation of the PDL stiffness and how to alter it. The R00 phase wil establish a deep understanding of the association between structure and function of the PDL and will develop a mechanism to control PDL function by structural modifications. This project includes a well-structured training program that provides theoretical course work, practical experience and protected research time during individualized specialty training in Orthodontics. The final result of this project, controlling tooth movement through modifications of cellular activities inside the PDL, will be a novel approach with the potential of greatly advancing the discipline of orthodontics and benefiting other medical disciplines as well.

 描述（由申请人提供）：通过PDL细胞操作获得的牙齿移动牙齿移动的能力对于它们适应不断变化的环境并因此对于它们的生存至关重要。牙周膜（PDL）在控制这种牙齿移动中起着核心作用。然而，尽管PDL的基本作用，功能机制和这个显着的组织的3D结构还没有完全理解。本研究旨在阐明牙周膜的结构-功能基础，从而为控制牙齿移动提供一种新的临床方法。载荷改变PDL内的纤维分布，以实现某些功能。例如，正畸负荷引起PDL纤维结构的变化，并引发一连串的骨重建，最终导致牙齿位置的变化。最近的研究表明，即使在正常的功能负荷下，PDL的结构和功能也是不均匀的;换句话说，牙齿功能控制PDL的结构。该项目的假设是，PDL结构的有意修改将引发周围骨骼的变化，并最终导致功能性牙齿变化。这一假设将在四个互补的具体目标中得到解决。指导阶段（K99）将在哈佛牙科医学院和波士顿大学牙科医学院进行，Bjorn Olsen博士作为导师，Leslie Will博士作为共同导师。在这一阶段的实验预计建立一个三维表征的胶原网络和细胞群体的小鼠磨牙PDL。为此，我们将利用一系列3D成像方法，我们将在microCT内使用独特的定制设备以及2光子和2次谐波成像。对于高分辨率结构分析，我们还将采用STORM和AirSEM方法。我们将通过不同的转基因小鼠品系来研究PDL中的细胞群，并利用原位杂交来研究基因表达水平和信号通路。跨学科的生物工程工具将用于PDL刚度的体外研究以及如何改变它。R 00阶段将建立对PDL结构和功能之间关联的深刻理解，并将开发通过结构修饰控制PDL功能的机制。该项目包括一个结构良好的培训计划，提供理论课程工作，实践经验和保护研究时间在个性化的专业培训正畸。该项目的最终结果是通过修改PDL内的细胞活动来控制牙齿移动，这将是一种新的方法，有可能大大推进牙齿矫正学的学科，并使其他医学学科受益。

项目成果

Nonuniformity in ligaments is a structural strategy for optimizing functionality.

• DOI: 10.1073/pnas.1807324115
• 发表时间: 2018-09-04
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Naveh GRS;Foster JE;Silva Santisteban TM;Yang X;Olsen BR
• 通讯作者: Olsen BR