Dentin-pulp dynamics of aging teeth
老化牙齿的牙本质-牙髓动力学
基本信息
- 批准号:10737859
- 负责人:
- 金额:$ 31.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:AddressAdultAffectAgeAgingArchitectureArteriesAutomobile DrivingBiologicalBiological AssayBiologyBloodCell AgingCellsCharacteristicsClinicalClinical TrialsCommunicationComplexConsultationsCrownsDehydrationDentalDental CareDental PulpDentinDentinogenesisElasticityElderlyEndodonticsEnzyme-Linked Immunosorbent AssayEsthesiaEvidence based practiceExtracellular MatrixFatigueFutureGoalsGrantGrowth FactorHardnessHealthHealthcareHumanHydration statusImmunofluorescence ImmunologicInfectionInjuryKnowledgeLifeLocationLongevityMaintenanceMechanicsMesenchymeMissionModelingMolecularMusNational Institute of Dental and Craniofacial ResearchNatural regenerationNerve FibersNeuritesNutrientOdontoblastsOperative Surgical ProceduresOral healthOrganPatientsPopulationPre-Clinical ModelProcessProtein SecretionProteinsProteomeProteomicsPublic HealthPulp CanalsPulp ChambersQuality of lifeRattusRegenerative capacityReportingResearchRiskRodentScaffolding ProteinSensoryTechniquesTechnologyTestingTherapeuticThickTimeTissuesTooth LossTooth regenerationTooth structureabsorptionage relatedagedalternative treatmentcalcificationconfocal imagingdensitydesignexperienceexperimental studyfollow-upfracture riskhuman old age (65+)improvedinnovationinterestmicroCTmineralizationmouse modelnanoindentationnerve supplyneurotrophic factorneurovascularneurovascular injurynovelolder patientpostnatal developmentpre-clinicalpreservationpreventregeneration potentialregenerativerepairedreparative capacityresponseresponse to injuryrestorative dentistryscaffoldsenescencestem cellstissue repairtomography
项目摘要
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.
项目概要/摘要
利用牙本质-牙髓复合物的再生能力的新策略的引入可能会使
人类有可能在一生中保留天然牙齿。研究表明
牙髓干细胞保持非凡的特性,可以为牙科护理提供临床选择
和恢复。然而,目前尚不清楚老年患者是否也能从这些技术中受益。
诺斯。该项目的长期目标是了解牙齿在整个成年过程中如何变化。
罩,以开发可以保持或增强牙齿健康并允许整个牙齿保持的治疗方法
寿命。我们的目标是分析年轻和年老啮齿动物磨牙的牙本质-牙髓界面,以定性
确定牙本质-牙髓复合体的再生能力如何随年龄变化。我们的中心假设
与年龄相关的 DP 间充质、脉管系统和神经支配的变化会改变分泌和利用
牙本质中生物活性蛋白 (BPiD) 的能力和牙髓衰老,以及牙髓获取机会的减少
BPiD,随着年龄的增长牙齿活力会降低。该项目的基本原理是建立一个详细的科学框架
牙齿老化和再生可能会发现活牙髓治疗的候选分子。中央hy-
假设将通过以下具体目标进行测试:1)识别牙本质中分泌的生物活性蛋白
随着年龄的增长而变化; 2) 分析牙齿随年龄的变化。在第一个目标下,从小到大的磨牙
将提取年老的大鼠,分为根部和冠部,并研磨以用于随后的蛋白质组学分析
牙本质成分。 ELISA 和/或免疫荧光将验证位置和丰度,以便识别
tify 感兴趣的分泌蛋白可以在损伤和/或再生过程中调节神经血管反应。
对于第二个目标,将对 3 个月和 20 个月大的小鼠的磨牙牙本质进行手术损伤并在
不同的时间点来评估:a) 使用纳米压痕测定的弹性和硬度; b) 矿化量
和通过显微计算机断层扫描 (micro-CT) 确定的密度; c) 牙髓神经血管损伤
基于共焦成像的响应。本申请中提出的研究具有创新性,因为它支持
使用应用于临床前小鼠模型的多种技术,全面了解牙齿如何老化
从年轻阶段到老年阶段。拟议的研究意义重大,因为它有望识别活髓
治疗和再生牙髓学候选者,用于继续研究和未来对患者进行临床试验
在人生的不同阶段。最终,这些知识有可能提供新的牙科治疗方法来帮助
患者保持牙齿健康并保留天然牙齿直至老年。
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
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Sarah Peters其他文献
Sarah Peters的其他文献
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{{ truncateString('Sarah Peters', 18)}}的其他基金
Mechanisms regulating afferent innervation in the dental pulp
调节牙髓传入神经支配的机制
- 批准号:
10186974 - 财政年份:2020
- 资助金额:
$ 31.5万 - 项目类别:
Mechanisms regulating afferent innervation in the dental pulp
调节牙髓传入神经支配的机制
- 批准号:
10214592 - 财政年份:2020
- 资助金额:
$ 31.5万 - 项目类别:
Mechanisms regulating afferent innervation in the dental pulp
调节牙髓传入神经支配的机制
- 批准号:
10453569 - 财政年份:2020
- 资助金额:
$ 31.5万 - 项目类别:
Mechanisms regulating afferent innervation in the dental pulp
调节牙髓传入神经支配的机制
- 批准号:
10599553 - 财政年份:2020
- 资助金额:
$ 31.5万 - 项目类别:
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