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

牙骨质的结构和生物学随年龄和疾病的变化

• 批准号: 10507239
• 负责人: Mariana Cavalcante Reis-Havlat
• 金额: $ 10.89万
• 依托单位: MARQUETTE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10507239
• 关键词: Achievement; Advisory Committees; Affect; Age; Aging; Animal Model; Anti-Inflammatory Agents; Area; Atomic Force Microscopy; Biochemical; Biocompatible Materials; Bioinformatics; Biological; Biology; Biomechanics; Cell physiology; Clinical; Collagen Fiber; Collagen Fibril; Data; Dental Cementum; Development Plans; Disease; Dissection; Educational workshop; Event; Excision; Exclusion; Extracellular Matrix; Faculty; Fiber; Foundations; High Prevalence; Human; IL8 gene; Immune system; Immunohistochemistry; Impairment; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Interleukin-1 beta; Interleukin-10; Interleukin-6; Kinetics; Knowledge; Ligature; Light; Longevity; Mastication; Measures; Mechanics; Mentors; MicroRNAs; Minerals; Modeling; Modification; Molecular; Morphology; Mus; Natural regeneration; Older Population; Oral health; Organ; Organism; Periodontal Diseases; Periodontal Ligament; Periodontic specialty; Periodontitis; Periodontium; Play; Positioning Attribute; Process; Property; Protein Analysis; Proteins; Proteomics; Regenerative capacity; Regenerative response; Research; Role; Series; Specimen; Spectrum Analysis; Stimulus; Structural Protein; Structure; System; TNF gene; Techniques; Therapeutic; Tissues; Tooth root structure; Tooth structure; age group; age related; aging population; alveolar bone; base; bone; career; career development; chemical property; chronic infection; cohort; cytokine; experience; feasibility testing; functional disability; improved; in vivo; innovation; mechanical behavior; mechanical load; mechanical properties; nano; prevent; regeneration potential; regenerative approach; screening; skills; treatment strategy

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.

项目摘要 衰老是一系列不可避免的渐进事件，影响所有生物体。结构和组成 矿化组织在老化过程中发生的变化会使其功能和再生恶化。 牙骨质是一种结缔矿化组织，通过附着来自牙骨质的胶原纤维来提供支撑。 牙周膜连接到牙齿，并通过在咀嚼期间吸收机械负荷而起作用。牙周 疾病是一种感染性慢性炎症性疾病，在老年人群中高度流行， 影响牙骨质的生物学和功能。然而，牙骨质的潜在功能特性 与衰老的关系还没有完全阐明。假设对组成和结构的修改将 随着老化降低牙骨质的功能性和再生，并潜在地增强牙骨质退化的进展。 牙周病的症状提出的目标包括确定生物化学，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 年龄（目标2）和描绘在体内的生物化学，物理机械和分子机制，在牙骨质 利用结扎诱导的牙周炎模型揭示衰老和牙周病的影响（目的3）。的 该提案的目的是整合生物体的重要事件（衰老和疾病），特别是其影响 口腔健康。这一建议是根据候选人的生物材料和基质生物学经验阐述的 并计划支持实现牙骨质生物学，结构和蛋白质分析， 和体内动物模型，以追求独立的研究生涯。一个经验丰富的咨询团队， 聚集在一起，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 导师），蛋白质分析和鼠牙周炎模型（Afsar Naqvi博士，共同导师），免疫组织化学 和再生（Xianghong Luan博士，共同导师），形态测量学（Jeffrey Toth博士，合作者），临床 牙周病学支持（VrisiisKofina博士）和ECM蛋白质组学和生物信息学（AlexandraNaba博士， 顾问）。职业发展计划旨在填补科学和专业技能的空白 与提案的目的有关。它由教学课程、讲习班和活动组成， 有组织的指导动态将使候选人实现特定的里程碑以获得 独立教师职位。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函数，以及这些过程的影响 关于牙骨质再生在这个提议中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的相互作用以及它们在环境中的可能作用奠定基础。 矿化组织的功能和再生。