Structure and Biology of the Cementum as a Function of Age and Disease

项目总结 衰老是影响所有生物的一系列不可避免的渐进事件。结构和构图 矿化组织在老化过程中发生的变化可能会恶化它们的功能和再生。 牙骨质是一种结缔组织矿化组织，通过附着来自牙周的胶原纤维来提供支持 牙周膜连接到牙齿，在咀嚼过程中通过吸收机械载荷发挥作用。牙周 疾病是一种感染性慢性炎症性疾病，在老年人中高度流行，并直接 影响牙骨质的生物学和功能。然而，牙骨质的基本功能特性 随着年龄的增长，这一现象还没有完全阐明。假设是，对组成和结构的修改将 随着年龄的增长，牙骨质的功能和再生能力下降，并可能促进牙骨质的进展。 牙周病。建议的目标包括确定生化、结构和机械 老化牙骨质的特征(目标1)，将牙周受累牙骨质的状态定义为 AGE(目标2)和描述牙骨质的体内生化、物理机械和分子机制 采用结扎法建立牙周炎模型，揭示衰老与牙周病的关系(目的3)。这个 这项提案的目的是综合生物的重要事件(衰老和疾病)，特别是它们的影响 在口腔健康方面。这项建议是基于候选人的生物材料和基质生物学经验而制定的 并计划支持获得牙骨质生物学、结构和蛋白质分析方面的专门技能， 并在活体动物模型上追求独立的研究事业。一支经验丰富的顾问团队 提供牙齿超微结构和生物力学方面的专业知识(Ana Bedran-Russo博士，主要 Mentor)、蛋白质分析与小鼠牙周炎模型(Afsar Naqvi博士，共同导师)、免疫组织化学 和再生(向红博士，共同导师)，形态计量学(Jeffrey Toth博士，合作者)，临床 牙周支持(Vrisiis Kofina博士)和ECM蛋白质组学和生物信息学(Alexandra Naba博士， 顾问)。职业发展计划的结构是为了在科学和专业技能的差距中取得进展 与提案的目标有关。它是由教学课程、研讨会和活动相结合组成的 有组织的指导动态将允许候选人实现特定的里程碑，以获得 独立教员职位。拟议目标的完成将揭示该结构的未知领域， 牙骨质的生物学和生物力学作为年龄和疾病的功能，以及这些过程的影响 关于牙骨质再生。这一建议阐明了牙骨质老化的潜在分子机制 可以为理解矿物与基质之间的相互作用及其在土壤中的可能作用奠定基础 矿化组织的功能和再生。

PROJECT SUMMARY Aging is an inevitable progressive series of events that effect all living organisms. Structural and compositional changes that occur to mineralized tissues during aging can deteriorate their function and regeneration. Cementum is a connective mineralized tissue that provides support, by attaching collagen fibrils from the periodontal ligament to the tooth, and function by absorbing mechanical loads during mastication. Periodontal disease is an infections chronic inflammatory condition that is highly prevalent in the older population and directly effects the biology and function of the cementum. However, the underlying functional properties of cementum with aging are not fully elucidated. The hypothesis is that modifications to the composition and structure will degrade the functionality and regeneration of the cementum with aging, and potentially enhance the progression of periodontal disease. The proposed aims consist of identifying the biochemical, structural, and mechanical features of the aging cementum (Aim 1), defining the state of periodontally involved cementum as a function of age (Aim 2) and delineating in vivo biochemical, physico-mechanical and molecular mechanisms in cementum to unveil the impact of aging and periodontal disease using ligature-induced periodontitis model (Aim 3). The aims of this proposal integrate important events (aging and disease) of living organisms, in particular their effects in oral health. This proposal is elaborated based on the candidate’s biomaterials and matrix biology experience and plans to support the achievement of specialized skills in cementum biology, structural and protein analysis, and in vivo animal models to pursue an independent research career. An experienced advisory team was assembled to provide expertise in tooth ultrastructure and biomechanics (Dr. Ana Bedran-Russo, primary mentor), protein analysis and murine periodontitis model (Dr. Afsar Naqvi, co-mentor), immunohistochemistry and regeneration (Dr. Xianghong Luan, co-mentor), morphometrics (Dr. Jeffrey Toth, collaborator), clinical periodontics support (Dr. Vrisiis Kofina) and ECM proteomics and bioinformatics (Dr. Alexandra Naba, consultant). The career development plan is structured to advance in the gaps of scientific and professional skills related to the aims of the proposal. It is composed of didactic courses, workshops and activities that combined with an organized mentoring dynamic will allow the candidate to achieve specific milestones to obtain an independent faculty position. The completion of the proposed aims will reveal uncharted areas of the structure, biology and biomechanics of the cementum as a function of age and disease, and the impact of these processes on cementum regeneration. Potential molecular mechanisms of cementum aging elucidated in this proposal could build a foundation for understanding mineral-to-matrix interactions and their probable roles in the functionality and regeneration of mineralized tissues.