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

摘要： 牙齿一生都在高重复咀嚼载荷下工作。它们需要迅速适应当地的食物 不同的大小和一致性，以实现有效的咀嚼过程。这一快速适应 这种能力是由一种独特的软组织提供的，它将牙齿连接到牙槽骨，即牙周膜 (PDL)。因此，牙周韧带对于牙齿的正常功能和存活至关重要。目前，有不同的 不同程度修复牙齿和牙槽骨结构的解决方案，但目前还没有可预测的方法 恢复PDL。这项提议将为PDL的再生治疗建立一个平台。PDL是一种 不均匀的组织，我们最近在最冠状部分发现了致密的胶原网的独特结构 并创造了术语密集项圈。该区域由密集、短的水平纤维组成，具有 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 与PDL中的分叉区相比，致密环的硬度以及独特的组成。 因此，我们假设致密的颈圈是牙齿整体稳定性的主要因素，因此 对致密环结构的任何损伤都会影响整个PDL功能。为了检验这一假设，我们将 采取多学科的方法研究这种组织的结构和功能以及它在整个 牙周膜功能与牙齿稳定性。我们将生成该区域的ECM和细胞轮廓的基线 用定位蛋白质组学和质量细胞术与PDL中的其他区域进行比较。我们将测量 用高频原子力显微镜测量致密环的力学性能和原位加载的牙齿移动 设备，我们将使用一种新的原位拉曼光谱和我们的显微CT来解开胶原结构 基于软组织成像的方法。我们将结合这些尖端方法，利用非固定的 样本具有最小的剖分，以使样本收集与其3D结构环境。然后我们将测试 不同干预措施对密环结构完整性的影响我们将使用 改良小鼠前牙周炎模型和正畸牙移动模型 密实领圈的力学性能以基线为主。在最后阶段，我们将确定一种方法来加强 致密的项圈，增加牙齿的稳定性。这项提议将决定密环在牙齿中的作用 稳定性以及致密项圈的结构变化与整体PDL功能之间的关联。多数 重要的是，拆解PDL内特定区域的结构和功能将为 结构性干预以加强这一区域，并控制整个牙周膜功能和牙齿稳定性。这 该提案将为不同牙科领域的范式转变奠定基础，如正畸、牙齿创伤和 牙周病。

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.