Dentin-pulp dynamics of aging teeth

老化牙齿的牙本质-牙髓动力学

• 批准号: 10737859
• 负责人: Sarah Peters
• 金额: $ 31.5万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10737859
• 关键词: Address; Adult; Affect; Age; Aging; Architecture; Arteries; Automobile Driving; Biological; Biological Assay; Biology; Blood; Cell Aging; Cells; Characteristics; Clinical; Clinical Trials; Communication; Complex; Consultations; Crowns; Dehydration; Dental; Dental Care; Dental Pulp; Dentin; Dentinogenesis; Elasticity; Elderly; Endodontics; Enzyme-Linked Immunosorbent Assay; Esthesia; Evidence based practice; Extracellular Matrix; Fatigue; Future; Goals; Grant; Growth Factor; Hardness; Health; Healthcare; Human; Hydration status; Immunofluorescence Immunologic; Infection; Injury; Knowledge; Life; Location; Longevity; Maintenance; Mechanics; Mesenchyme; Mission; Modeling; Molecular; Mus; National Institute of Dental and Craniofacial Research; Natural regeneration; Nerve Fibers; Neurites; Nutrient; Odontoblasts; Operative Surgical Procedures; Oral health; Organ; Patients; Population; Pre-Clinical Model; Process; Protein Secretion; Proteins; Proteome; Proteomics; Public Health; Pulp Canals; Pulp Chambers; Quality of life; Rattus; Regenerative capacity; Reporting; Research; Risk; Rodent; Scaffolding Protein; Sensory; Techniques; Technology; Testing; Therapeutic; Thick; Time; Tissues; Tooth Loss; Tooth regeneration; Tooth structure; absorption; age related; aged; alternative treatment; calcification; confocal imaging; density; design; experience; experimental study; follow-up; fracture risk; human old age (65+); improved; innovation; interest; microCT; mineralization; mouse model; nanoindentation; nerve supply; neurotrophic factor; neurovascular; neurovascular injury; novel; older patient; postnatal development; pre-clinical; preservation; prevent; regeneration potential; regenerative; repaired; reparative capacity; response; response to injury; restorative dentistry; scaffold; senescence; stem cells; tissue repair; tomography; Address; Adult; Affect; Age; Aging; Architecture; Arteries; Automobile Driving; Biological; Biological Assay; Biology; Blood; Cell Aging; Cells; Characteristics; Clinical; Clinical Trials; Communication; Complex; Consultations; Crowns; Dehydration; Dental; Dental Care; Dental Pulp; Dentin; Dentinogenesis; Elasticity; Elderly; Endodontics; Enzyme-Linked Immunosorbent Assay; Esthesia; Evidence based practice; Extracellular Matrix; Fatigue; Future; Goals; Grant; Growth Factor; Hardness; Health; Healthcare; Human; Hydration status; Immunofluorescence Immunologic; Infection; Injury; Knowledge; Life; Location; Longevity; Maintenance; Mechanics; Mesenchyme; Mission; Modeling; Molecular; Mus; National Institute of Dental and Craniofacial Research; Natural regeneration; Nerve Fibers; Neurites; Nutrient; Odontoblasts; Operative Surgical Procedures; Oral health; Organ; Patients; Population; Pre-Clinical Model; Process; Protein Secretion; Proteins; Proteome; Proteomics; Public Health; Pulp Canals; Pulp Chambers; Quality of life; Rattus; Regenerative capacity; Reporting; Research; Risk; Rodent; Scaffolding Protein; Sensory; Techniques; Technology; Testing; Therapeutic; Thick; Time; Tissues; Tooth Loss; Tooth regeneration; Tooth structure; absorption; age related; aged; alternative treatment; calcification; confocal imaging; density; design; experience; experimental study; follow-up; fracture risk; human old age (65+); improved; innovation; interest; microCT; mineralization; mouse model; nanoindentation; nerve supply; neurotrophic factor; neurovascular; neurovascular injury; novel; older patient; postnatal development; pre-clinical; preservation; prevent; regeneration potential; regenerative; repaired; reparative capacity; response; response to injury; restorative dentistry; scaffold; senescence; stem cells; tissue repair; tomography

PROJECT SUMMARY/ABSTRACT The introduction of new strategies harnessing the regenerative capacity of the dentin-pulp complex may make it possible for humans to retain their natural teeth throughout their lifespan. Research has demonstrated that dental pulp stem cells maintain extraordinary characteristics that can provide clinical options for dental care and restoration. However, it remains unknown whether older patients are also able to benefit from these tech- nologies. The long-term goal of this project is to gain an understanding of how teeth change throughout adult- hood in order to develop treatments that can preserve or enhance tooth health and permit retention throughout the lifespan. Our objective is to analyze the dentin-pulp interface in young and old rodent molars to qualitatively determine how the regenerative capacity of the dentin-pulp complex changes with age. Our central hypothesis is that age-related changes to the DP mesenchyme, vasculature, and innervation alter the secretion and avail- ability of bioactive proteins in dentin (BPiD) and that pulpal senescence, in combination with reduced access to BPiD, reduces tooth vitality with age. The rationale for this project is that a detailed scientific framework of tooth aging and regeneration is likely to uncover molecular candidates for vital pulp therapies. The central hy- pothesis will be tested with the following specific aims: 1) Identify secreted bioactive proteins in dentin that change with age; and 2) Analyze age-dependent changes in teeth. Under the first aim, molars from young and old rats will be extracted, divided into root and crown portions, and milled for subsequent proteomic analyses of the dentin composition. ELISA and/or immunofluorescence will verify location and abundance in order to iden- tify secreted proteins of interest that could regulate neurovascular responses during injury and/or regeneration. For the second aim, mouse molar dentin in 3- and 20-month mice will be surgically damaged and analyzed at varying time points to assess: a) elasticity and hardness using nanoindentation assays; b) mineralized volume and density determined by microcomputed tomography (micro-CT); and c) dental pulp neurovascular injury responses based on confocal imaging. The research proposed in this application is innovative because it pro- vides a comprehensive view of how teeth age using several techniques applied to preclinical murine models from young and elderly stages. The proposed research is significant because it is expected to identify vital pulp therapy and regenerative endodontics candidates for continued research and future clinical trials with patients in different stages of life. Ultimately, such knowledge has the potential to offer new dental treatments to help patients maintain their dental health and retain their natural teeth into old age.

项目摘要/摘要 引入了利用牙本质 - 普尔普综合体再生能力的新策略可能会导致 人类在整个生命周期中都可以保留其自然牙齿。研究表明 牙髓干细胞保持非凡特征，可以为牙科护理提供临床选择 和恢复。但是，尚不清楚老年患者是否也能够从这些技术中受益 - 科学。该项目的长期目标是了解整个成年人的牙齿如何变化 - 引擎盖以开发可以保留或增强牙齿健康并允许保留的治疗方法 寿命。我们的目的是分析年轻和老啮齿动物磨牙的牙本质 - 羽毛界面以定性 确定牙本质-Pulp复合物的再生能力如何随着年龄的增长而变化。我们的中心假设 是否与年龄相关的DP间充质，脉管系统和神经的变化改变了分泌和利用 生物活性蛋白在牙本质（BPID）中的能力和牙髓衰老的能力，并结合使用降低 BPID会随着年龄的增长而降低牙齿活力。该项目的理由是一个详细的科学框架 牙齿衰老和再生可能会发现重要的纸浆疗法的分子候选者。中央 将以以下特定目的对植物进行测试：1）识别牙本质中的分泌生物活性蛋白 随着年龄的变化； 2）分析牙齿依赖年龄的变化。在第一个目标下，来自Young和 将提取旧大鼠，分为根部和牙冠部分，并进行铣削以进行随后的蛋白质组学分析 牙本质组成。 ELISA和/或免疫荧光将验证位置和丰度，以便 感兴趣的分泌蛋白质可以调节受伤和/或再生期间神经血管反应。 为了第二个目标，将在3个月和20个月的小鼠中进行手术损伤和分析的小鼠摩尔牙本质。 评估的不同时间点：a）使用纳米构造测定的弹性和硬度； b）矿化体积 和密度通过微型层析成像（Micro-CT）确定；和c）牙髓神经血管损伤 基于共聚焦成像的响应。该应用程序中提出的研究具有创新性 综合视图对牙齿的使用方式使用多种技术应用于临床前鼠模型 来自年轻和老年阶段。拟议的研究很重要，因为它有望识别重要的牙髓 治疗和再生牙髓病候选者，可继续研究和未来的临床试验 在生活的不同阶段。最终，这种知识有可能提供新的牙科治疗来帮助 患者保持牙齿健康，并将其自然牙齿保留到老年。