Functional Competence of a Dentoalveolar Fibrous Joint in Vertebrates

脊椎动物牙槽纤维关节的功能能力

• 批准号: 9765908
• 负责人: Sunita P Ho
• 金额: $ 38.16万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-09 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9765908
• 关键词: Age; Animals; Biological; Biological Assay; Biological Process; Biomechanics; Cells; Clinical; Competence; Complex; Data; Dental Cementum; Dentists; Detection; Diet; Electron Microscopy; Equilibrium; Exposure to; Failure; Female; Fluorescence; Food; Frequencies; Genes; Guidelines; Human; Image; In Situ; Intervention; Jaw; Joints; Lead; Maps; Mastication; Maxilla; Measures; Mediating; Methods; Minerals; Modeling; Molecular; Morphology; Mus; Muscle; Musculoskeletal System; Orthodontic; Orthodontics; Outcome; Parents; Pathologic; Periodontal Ligament; Phenotype; Physiological; Process; Property; Proteins; Rattus; Recovery; Recovery of Function; Research; Risk; Rodent; Scanning; Site; Soft Diet; Stimulus; Stress; Structure; TNFSF11 gene; Therapeutic; Time; Tissues; Tooth Crowns; Tooth Movement; Tooth structure; Transgenic Mice; Vertebrates; X-Ray Computed Tomography; age group; age related; alveolar bone; asporin; bone; differential expression; digital; in vivo; joint function; joint stiffness; male; mouse model; preservation; response; scleraxis; spatiotemporal; transmission process

ABSTRACT A variety of biomechanical stimuli are directed on the dentoalveolar fibrous joint (DAJ) of the masticatory complex (e.g. chewing on softer diet (SD), therapeutic loads from orthodontic interventions), and can result in local abnormal deformations and adaptive processes that can lead to aberrant function [1-7]. A systematic study of the effect of SD on the tooth-crown revealed significant age-related shifts in biological processes in the periodontal complex (R01DE022032 02/2012-01/2018). Thus, recovery of an adapting joint to its original stiffness is compromised with age, but the question remained: when the joint is exposed to prolonged aberrant loads, what is the optimal age range for the joint to recover to its baseline biomechanics should the aberrant load be substituted with physiologic loads (hard diet (HD))? What is the age range beyond which joint biomechanics are irreversible? Data from the recovery model (RM) (mice raised to various time points on SD and switched to HD), will help determine the age range for which functional competence of the joint is maintained, and help predict when clinical intervention simulated through an experimental tooth movement (ETM) model is most effective. ETM will also help in identifying the intended reversal of natural biological processes [8] at the strain-amplified sites of the PDL-entheses. Hypothesis: The functional competence of the DAJ can be identified as age-related gradients in biological expressions (ΔBE/Δage) and joint stiffness (ΔS/Δage). From a translational perspective, ETM is effective in an age range that demonstrates minima in ΔS/Δage. Proposed aims will include: Aim 1: To assess the recovery of functional competence of adapting fibrous joints with age. Functional competence of an adapted joint will be determined by its ability to resist shifts in magnitudes and frequencies of biomechanical loads without subsequent pathologic function [9]; to-date no such data exist. Functional competence will be determined from digital spatiotemporal maps of changes in periodontal ligament (PDL)-spaces, tooth-bone morphology and joint stiffness (ΔS/Δage) with age from SD, HD, RM groups. The RM will identify an age range to optimize preservation of the fibrous joint. Aim 2: To assess the mechanobiological processes of an adapting fibrous joint with age. Spatiotemporal shifts in biological expressions (BE) (ΔBE/Δage – genes and matrix proteins) at the bone, cementum, and the PDL-entheses from respective age groups will be mapped. Differentially expressed genes, and mineral forming and resorbing matrix factors at PDL-entheses and the PDL at widened and narrowed regions with age for three groups (SD, HD, RM) will be correlated. AIM 3: To assess the effect of a proposed age range on experimental tooth movement resulting in long-term functional competence. Outcome physicochemical and biological measures will be the same as in Aims 1 and 2 but on ETM group [10] before, during, and after the proposed age range from the RM in Aims 1 and 2. The intended reversal of natural biological process at the strain-amplified PDL-entheses in the ETM model also will be investigated.

抽象的 多种生物力学刺激针对咀嚼肌的牙槽纤维关节 (DAJ) 复杂（例如咀嚼较软的饮食（SD）、正畸干预的治疗负荷），并可能导致 局部异常变形和适应性过程可能导致功能异常[1-7]。一个系统的 SD 对牙冠影响的研究揭示了与年龄相关的生物过程的显着变化 牙周复合体（R01DE022032 02/2012-01/2018）。因此，将适配接头恢复至其原始状态 刚度会随着年龄的增长而减弱，但问题仍然存在：当关节长期处于异常状态时 负载，如果异常，关节恢复到其基线生物力学的最佳年龄范围是多少？ 负荷可以用生理负荷代替（硬饮食（HD））吗？关节超过什么年龄范围 生物力学是不可逆的？来自恢复模型 (RM) 的数据（将小鼠饲养到 SD 上的各个时间点） 并切换到 HD），将有助于确定关节功能能力的年龄范围 保持，并帮助预测何时通过实验性牙齿移动模拟临床干预 (ETM) 模型是最有效的。 ETM 还将有助于确定天然生物的预期逆转 PDL 附着点应变放大位点的过程 [8]。假设：功能能力 DAJ 可以被识别为生物表达中与年龄相关的梯度 (ΔBE/Δage) 和关节 刚度（ΔS/Δ年龄）。从转化的角度来看，ETM 在年龄范围内是有效的，这表明 ΔS/Δage 中的最小值。拟议的目标将包括： 目标 1：评估功能能力的恢复情况 随着年龄的增长，纤维关节逐渐适应。适应关节的功能能力将由其能力决定 抵抗生物力学负荷的大小和频率的变化，而不会产生后续的病理功能 [9]；迄今为止不存在此类数据。功能能力将根据数字时空地图确定 牙周膜（PDL）间隙、牙骨形态和关节刚度（ΔS/Δage）随年龄的变化 来自 SD、HD、RM 组。 RM 将确定年龄范围以优化纤维关节的保存。目的 图 2：评估纤维关节随年龄变化的机械生物学过程。时空 骨、牙骨质和牙骨质的生物表达 (BE)（ΔBE/Δage – 基因和基质蛋白）的变化 来自各个年龄组的 PDL-enthese 将被绘制出来。差异表达基因和矿物质形成 以及 PDL 附着点处的再吸收基质因子以及随年龄增长而扩大和缩小的 PDL 区域的基质因子 组（SD、HD、RM）将相关。目标 3：评估提议的年龄范围对 实验性牙齿移动导致长期功能能力。结果 理化和生物测量与目标 1 和 2 相同，但针对 ETM 组 [10] 在目标 1 和 2 中建议的 RM 年龄范围之前、期间和之后。预期的逆转 ETM 模型中应变扩增 PDL 附着点的自然生物过程也将被研究。