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性事件，这些事件影响了所有生物体。结构和成分 衰老过程中矿化组织发生的变化可以确定它们的功能和再生。 Cementum是一种连接的矿化组织，可通过连接胶原蛋白原纤维的矿化组织 牙齿的牙周韧带，并通过在咀嚼过程中吸收机械载荷来发挥作用。牙周 疾病是一种感染慢性炎症状况，在老年人群中高度普遍，直接 影响牙骨质的生物学和功能。但是，胶质的基本功能特性 随着衰老未充分阐明。假设是对组成和结构的修改将 随着衰老的降低胶质的功能和再生，并有可能增强进展 牙周疾病。所提出的目的包括识别生化，结构和机械 衰老的牙骨质的特征（AIM 1），定义了牙周涉及的牙骨质状态的函数 年龄（AIM 2）和在牙骨质中描绘体内生化，物理机械和分子机制 通过结扎诱导的牙周炎模型揭示衰老和牙周疾病的影响（AIM 3）。 该提案的目的整合了生物体的重要事件（衰老和疾病），尤其是它们的影响 在口腔健康中。该建议是根据候选人的生物材料和基质生物学经验详细阐述的 并计划支持实现牙骨质生物学，结构和蛋白质分析方面的专业技能， 并在体内动物模型从事独立研究职业。经验丰富的咨询团队是 组装以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 蛋白质分析和鼠牙周炎模型（Afsar Naqvi博士，同事），免疫组织化学 和再生（Co-enghong Luan博士），Morphometrics（合作者Jeffrey Toth博士），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在科学和专业技能的差距中发展 与该提案的目的有关。它由结合的教学课程，研讨会和活动组成 具有有组织的心理动态，将使候选人达到特定的里程碑以获得 独立教师职位。拟议的目标的完成将揭示结构的未知区域， 牙骨质的生物学和生物力学是年龄和疾病的功能，以及这些过程的影响 关于牙骨质再生。在此提案中阐明的牙骨质老化的潜在分子机制 可以为理解矿物与矩阵的相互作用及其在 矿化组织的功能和再生。