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（通过应用程序提供）：由PDL细胞操纵得出的牙齿运动，牙齿移动的能力对于适应不断变化的环境以及因此生存至关重要。牙周韧带（PDL）在控制这种牙齿运动方面具有核心作用。但是，尽管PDL具有基本作用，但该非凡组织的功能机制和3D结构尚未完全了解。拟议的研究旨在阐明PDL的结构功能基础，并通过生成一种新的临床方法来控制牙齿运动。负载更改PDL内部的纤维分布，以实现某些功能。例如，正畸负载会导致PDL纤维结构的变化，并触发一系列骨骼重塑，有时会导致牙齿位置发生变化。最近显示，即使在正常功能载荷下，PDL的结构和功能也不统一。换句话说，牙齿功能控制PDL的结构。该提出的项目的假设是，PDL结构中的故意修改将触发周围骨骼的变化，并最终触发牙齿的变化。该假设将以四个完整的特定目的解决。 Mendored阶段（K99）将与Bjorn Olsen博士一起担任导师，Leslie Will博士担任哈佛牙科医学院和波士顿大学牙科医学学院的同事。预计在此阶段的实验将建立胶原蛋白网络和小鼠摩尔牙齿PDL的细胞种群的3D表征。为此，我们将利用3D成像方法的武器库，我们将在Microct以及2个光子和第二次谐波成像中使用独特的定制设备。对于高分辨率结构分析，我们还将采用风暴和AIRSEM方法。我们将跨越不同遗传修饰的小鼠菌株，以研究PDL中的细胞种群，我们将利用原位杂交研究基因表达水平以及信号传导途径。跨学科，生物工程工具将用于PDL刚度的体外投资以及如何改变它。 R00阶段将对PDL的结构和功能之间的关联建立深刻的理解，并将开发一种通过结构修饰来控制PDL功能的机制。该项目包括一个结构良好的培训计划，该计划在正畸学的个性化专业培训期间提供理论课程工作，实践经验和受保护的研究时间。该项目的最终结果是通过PDL内部的细胞活动的修改来控制牙齿运动，这将是一种新颖的方法，具有巨大的促进正畸学科并使其他医学学科受益的潜力。

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