Tooth Movement derived by PDL Cellular Manipulations

PDL 细胞操作衍生的牙齿移动

基本信息

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
项目类别：
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

项目摘要

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）：PDL 细胞操作产生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至关重要，因此牙周膜 (PDL) 在控制牙齿方面发挥着核心作用。然而，尽管 PDL 具有基本作用，但这种非凡组织的功能机制和 3D 结构尚未完全了解。本研究旨在阐明 PDL 的结构功能基础。通过这样做，可以产生一种新的临床方法来控制牙齿移动，从而改变 PDL 内的纤维分布，以实现某些功能。例如，正畸负荷会导致 PDL 纤维结构发生变化，并最终引发一系列骨重塑。最近的研究表明，即使在正常的功能负荷下，PDL 的结构和功能也不一致；换句话说，牙齿的功能控制着 PDL 的结构。项目是有意修改的PDL 结构的变化将引发周围骨骼的变化，并最终引发功能性牙齿的变化。指导阶段 (K99) 将由 Bjorn Olsen 博士作为导师，Leslie Will 博士作为指导者进行。哈佛大学牙科医学院和波士顿大学牙科医学院的共同导师预计此阶段的实验将建立小鼠臼齿 PDL 的胶原蛋白网络和细胞群的 3D 表征。，我们将利用3D 成像方法库中，我们将在 microCT 内使用独特的定制设备以及 2 光子和二次谐波生成成像，为了进行高分辨率结构分析，我们还将采用 STORM 和 AirSEM 方法。我们将利用小鼠品系来研究 PDL 中的细胞群，我们将利用原位杂交来研究基因表达水平以及信号通路。跨学科、生物工程工具将用于体外研究。 R00 阶段将深入了解 PDL 的结构和功能之间的关联，并开发一种通过结构修改来控制 PDL 功能的机制。正畸学个性化培训专业期间的理论课程工作、实践经验和受保护的研究时间，该项目的最终结果是通过改变 PDL 内的细胞活动来控制牙齿移动，这将是一种具有极大推进学科发展潜力的新颖方法。正畸和也有利于其他医学学科。