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.

项目概要 衰老是影响所有生物体结构和组成的一系列不可避免的渐进事件。 衰老过程中矿化组织发生的变化会损害其功能和再生。 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。 牙周韧带连接到牙齿，并通过吸收咀嚼过程中的机械负荷而发挥作用。 该疾病是一种感染性慢性炎症性疾病，在老年人群中非常普遍，并且直接 影响牙骨质的生物学和功能然而，牙骨质的潜在功能特性。 随着老化的发生尚未完全阐明。假设是成分和结构的改变会发生。 随着年龄的增长，牙骨质的功能和再生会降低，并可能加速进展 所提出的目标包括确定牙周病的生化、结构和机械特征。 老化牙骨质的特征（目标 1），将牙周病牙骨质的状态定义为以下函数： 年龄（目标 2）并描述牙骨质的体内生化、物理机械和分子机制 使用结扎诱导的牙周炎模型揭示衰老和牙周病的影响（目标 3）。 该提案的目标整合了生物体的重要事件（衰老和疾病），特别是它们的影响 该提案是根据候选人的生物材料和基质生物学经验详细阐述的。 并计划支持获得牙骨质生物学、结构和蛋白质分析方面的专业技能， 和体内动物模型，以追求独立的研究生涯。 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，初级 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（栾向红博士，共同导师），形态计量学（Jeffrey Toth 博士，合作者），临床 牙周学支持（Vrisiis Kofina 博士）和 ECM 蛋白质组学和生物信息学（Alexandra Naba 博士， 职业发展计划旨在弥补科学和专业技能的差距。 它由教学课程、研讨会和活动组成。 通过有组织的指导动态，候选人将能够实现特定的里程碑，从而获得 独立教员职位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 关于本提案中阐明的牙骨质老化的潜在分子牙骨质机制 可以为理解矿物与基质的相互作用及其在 矿化组织的功能和再生。