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 各种生物力学刺激针对咀嚼性的齿状肺泡关节（DAJ） 复合物（例如，咀嚼柔软饮食（SD），正畸干预措施的治疗负荷），可以导致 可能导致异常功能的局部异常变形和自适应过程[1-7]。系统 SD对牙冠的影响的研究表明，生物学过程中与年龄相关的显着转移 牙周综合体（R01DE022032 02/2012-01/2018）。那是恢复适应关节的原始关节 刚度随着年龄的增长而损害，但问题仍然存在：当关节暴露于长时间的异常时 负载，如果异常，关节恢复到基线生物力学的最佳年龄范围是多少 负荷被生理负荷（硬饮食（HD））取代？超出联合的年龄范围是多少 生物力学是不可逆转的吗？来自恢复模型（RM）的数据（将小鼠提高到SD上的各个时间点 切换到高清）将有助于确定关节功能能力的年龄范围 维护并有助于预测何时通过实验牙齿运动模拟临床干预措施 （ETM）模型是最有效的。 ETM还将有助于识别自然生物学的预期逆转 PDL-嵌入的应变放大位点的过程[8]。假设： 可以将DAJ识别为生物表达（ΔBE/ΔAge）和关节中与年龄相关的梯度 刚度（δs/ΔAge）。从翻译的角度来看，ETM在证明的年龄范围内有效 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 随着年龄的增长调整纤维关节。适应关节的功能能力将取决于其能力 抵抗磁化量和生物力学负载频率的变化，而没有随后的病理功能 [9];迄今为止不存在此类数据。功能能力将从数字时空图确定 随着年龄的增长 来自SD，HD，RM组。 RM将确定一个年龄范围，以优化纤维接头的保存。目的 2：评估随着年龄的增长纤维接头的机械生物学过程。时空 生物表达（BE）（ΔBE/ΔAge - 基因和基因蛋白）的变化在骨骼，骨质和骨质上 将映射来自相对年龄组的PDL-嵌入。差异表达的基因和矿物质形成 并在PDL-嵌套处的矩阵因子以及随着年龄的增长和狭窄区域的PDL持续三个 组（SD，HD，RM）将相关。目标3：评估拟议年龄范围对 实验性牙齿运动导致长期功能能力。结果 物理和生物学措施将与目标1和2中相同，但在ETM组上[10] 在拟议的年龄之前，期间和之后，目标是1和2的RM。 ETM模型中应变放大的PDL-嵌入的自然生物过程也将进行研究。