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: 10686415
• 负责人: Gili Rina Naveh
• 金额: $ 55.22万
• 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/10686415
• 关键词: 3-Dimensional; Address; Affect; Aging; Apical; Area; Blood Vessels; Bone structure; Clinical; Coin; Collagen; Collagen Type VI; Complex; Crosslinker; 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; Predisposition; 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

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： 牙齿在一生中都在高重复咀嚼负荷下发挥作用。他们需要快速适应食物 不同的尺寸和稠度，以实现有效的咀嚼过程。这种快速适应 这种能力是由将牙齿连接到牙槽骨的独特软组织（牙周韧带）提供的 （PDL）。因此，PDL 对于牙齿的正常功能和存活至关重要。目前，有不同 不同程度恢复牙齿和牙槽骨结构的解决方案，但不存在可预测的方法 恢复 PDL。该提案将为 PDL 再生治疗建立一个平台。 PDL 是一个 不均匀的组织，我们最近在最冠状部分发现了一种独特的致密胶原蛋白网络结构 PDL 并创造了“密集领”一词。该区域由密集的短水平纤维组成， 与牙齿的自然漂移方向相对应的方向性偏好。我们最近的研究表明更高 与 PDL 中的分叉区域相比，致密环的刚度以及独特的成分。 因此，我们假设致密环是牙齿整体稳定性的主要贡献者，因此 致密领结构的任何损伤都会影响整个 PDL 功能。为了检验这个假设，我们将 采用多学科方法研究该组织的结构和功能及其在整个系统中的作用 PDL 功能和牙齿稳定性。我们将生成该区域的 ECM 和细胞概况的基线 使用局部蛋白质组学和质谱流式技术与 PDL 中的其他区域进行比较。我们将测量 使用高频 AFM 的致密轴环的机械性能和使用原位加载的牙齿移动性 设备，我们将使用新型原位拉曼光谱和我们的 microCT 揭示胶原蛋白结构 基于软组织成像的方法。我们将利用 unfixed 将这些前沿方法结合起来 具有最小切片的样本，以便能够通过其 3D 结构上下文收集样本。然后我们将测试 对致密环结构完整性的不同干预措施对牙齿活动度的影响。我们将使用一个 改良的牙周炎前模型和小鼠正畸牙齿移动模型并比较结构和 密环的机械性能达到基线。在最后阶段，我们将确定一种加强方法 致密的颈圈可增加牙齿的稳定性。该提案将确定致密环在牙齿中的作用 稳定性以及致密领结构变化与整体 PDL 功能之间的关联。最多 重要的是，解开 PDL 内特定区域的结构和功能将为 结构干预措施可强化该区域并控制整个 PDL 功能和牙齿稳定性。这 该提案将为不同牙科领域的范式转变奠定基础，例如正畸、牙科创伤和 牙周病学。