Non uniformity in the PDL: structure and function of the dense collar

PDL 的不均匀性：致密环的结构和功能

• 批准号: 10296840
• 负责人: Gili Rina Naveh
• 金额: $ 54.06万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10296840
• 关键词: Address; Affect; Aging; Apical; Area; Blood Vessels; Bone structure; Clinical; Coin; Collagen; Collagen Type VI; Complex; Cytology; Cytometry; Dental; Devices; Extracellular Matrix; Fiber; Food; Frequencies; Generations; Health; Impairment; In Situ; Injury; Intervention; Link; Location; Mass Spectrum Analysis; Mastication; Measures; Methodology; Methods; Modeling; Movement; Orthodontic; Orthodontics; Outcome; Pathology; Patients; Periodontal Diseases; Periodontal Ligament; Periodontic specialty; Periodontitis; Plant Roots; Process; Proteomics; Raman Spectrum Analysis; Research; Riboflavin; Role; Sampling; Structure; Testing; Tissue imaging; Tissues; Tooth Mobility; Tooth Movement; Tooth Socket; Tooth structure; Translating; Trauma; Work; alveolar bone; base; bone; crosslink; density; dosage; functional restoration; in vivo Model; interdisciplinary approach; mechanical properties; microCT; mouse model; novel; novel strategies; preference; regenerative therapy; restoration; sample collection; second harmonic; soft tissue; three dimensional structure

ABSTRACT: Teeth function under high repetitive masticatory loads throughout lifetime. They need to quickly adapt to food in different sizes and consistencies in order to enable an efficient masticatory process. This quick adaptation capability is provided by a unique soft tissue that connects the tooth to the alveolar bone, the periodontal ligament (PDL). The PDL, therefore, is critical for proper tooth function and survival. At present, there are different solutions for restoring teeth and alveolar bone structure to different extents but no predictable methods exist for restoring the PDL. This proposal will establish a platform for a regeneration therapy for the PDL. The PDL is a non-uniform tissue, we recently identify a unique structure of dense collagen network at the most coronal part of the PDL and coined the term dense collar. This region is consists of dense, short horizontal fibers with a directionality preference that corresponds to natural drift direction of the tooth. Our recent studies show higher stiffness of the dense collar when compared to the furcation region in the PDL as well as unique composition. We therefore hypothesize that the dense collar is a central contributor to the overall tooth stability and therefore any impairment to the dense collar structure will affect the entire PDL function. To test this hypothesis we will take a multidisciplinary approach investigating the structure and function of this tissue and its role in the entire PDL function and tooth stability. We will generate a base line of the ECM and cellular profile of this region in comparison to other regions in the PDL using localized proteomics and mass cytometry. We will measure the mechanical properties of the dense collar using high frequency AFM and tooth mobility using an in-situ loading device and we will unravel the collagen structure using a novel in-situ Raman spectroscopy and our microCT based method for soft tissue imaging. We will combine theses cutting edge methodologies utilizing unfixed samples with minimal sectioning to enable sample collection with their 3D structural context. We will then test the effect of different interventions to the structural integrity of the dense collar on tooth mobility. We will use a modified pre-periodontitis model and orthodontic tooth movement in mice model and compare the structural and mechanical properties of the dense collar to the base line. In the last stage we will identify a method to strengthen the dense collar to increase tooth stability. This proposal will determine the role of the dense collar in tooth stability and the association between structural changes in the dense collar and overall PDL function. Most importantly, unraveling the structure and function of a specific region within the PDL will generate a platform for structural interventions to reinforce this region and control the entire PDL function and tooth stability. This proposal will lay the ground to a paradigm shift in different dental fields such as orthodontics, dental trauma, and periodontics.

抽象的： 在整个生命周期中，牙齿在高重复的咀嚼负荷下的功能。他们需要快速适应食物 不同的尺寸和一致性以实现有效的咀嚼过程。这种快速改编 能力由独特的软组织提供，该软组织将牙齿连接到牙槽骨（牙周韧带） （PDL）。因此，PDL对于适当的牙齿功能和存活至关重要。目前，有不同的 将牙齿和牙槽骨结构恢复到不同范围的解决方案，但没有可预测的方法 还原PDL。该提案将建立一个用于PDL再生疗法的平台。 PDL是一个 非均匀的组织，我们最近在最冠状的部分确定了密集胶原网络的独特结构 PDL并创造了术语致密的衣领。该区域由密集的短水平纤维组成 方向性偏好与牙齿的自然漂移方向相对应。我们最近的研究表明更高 与PDL中的毛囊区域以及独特的组成相比，密集项圈的刚度。 因此，我们假设密集的衣领是整体牙齿稳定性的核心贡献者，因此 对密集的衣领结构的任何损害都会影响整个PDL功能。为了检验这个假设，我们将 采用多学科的方法来研究该组织的结构和功能及其在整个中的作用 PDL功能和牙齿稳定性。我们将生成该区域的ECM的基线和蜂窝剖面 使用局部蛋白质组学和质量细胞仪与PDL中的其他区域进行比较。我们将衡量 使用高频AFM和牙齿迁移率使用原位载荷的机械性能 设备，我们将使用新型的原位拉曼光谱和我们的Microct拆开胶原蛋白结构 基于软组织成像的方法。我们将利用未固定的尖端方法结合这些尖端方法。 带有最小切片的样品，以允许其3D结构背景的样本收集。然后我们将测试 不同干预措施对密集项圈结构完整性对牙齿迁移率的影响。我们将使用一个 修饰的小鼠模型和正畸牙齿运动的修饰前牙齿运动模型，并比较结构和 密集衣领的机械性能到基线。在最后阶段，我们将确定一种加强的方法 致密的衣领以提高牙齿稳定性。该提议将确定密集项圈在牙齿中的作用 稳定性与密集衣领的结构变化与总体PDL功能之间的关联。最多 重要的是，阐明PDL内特定区域的结构和功能将为 结构性干预措施以加强该区域并控制整个PDL功能和牙齿稳定性。这 提案将在不同的牙科领域（例如正畸，牙科创伤和 牙周。