Functional Competence of a Dentoalveolar Fibrous Joint in Vertebrates

摘要 各种生物力学刺激是针对牙槽骨纤维关节（DAJ）的咀嚼 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 局部异常变形和自适应过程可能导致功能异常[1-7]。一个系统 SD对牙冠影响的研究显示， 牙周复合体（R 01 DE 022032 02/2012-01/2018）。因此，将适配接头恢复到其原始接头， 随着年龄的增长，刚度会受到影响，但问题仍然存在：当关节长期暴露在异常的 负荷，什么是最佳的年龄范围为关节恢复到其基线生物力学应该异常 用生理负荷（硬质饮食（HD））代替负荷？什么是年龄范围超过哪个关节 生物力学是不可逆的吗来自恢复模型（RM）的数据（SD时饲养至不同时间点的小鼠） 并切换到HD），将有助于确定关节功能能力的年龄范围， 保持，并帮助预测当通过实验性牙齿移动模拟临床干预时 (ETM)模型是最有效的。ETM还将有助于确定自然生物学的预期逆转， 在PDL-附着点的应变扩增位点处的过程[8]。假设： 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/Δage）。从翻译的角度来看，ETM在一个年龄范围内有效， ΔS/Δ年龄的最小值。拟议的目标将包括： 随着年龄的增长适应纤维关节。适应性关节的功能能力将取决于其能力 以抵抗生物力学载荷的幅度和频率的变化，而不产生随后的病理功能 [9];迄今为止没有这类数据。功能能力将从数字时空地图确定， 牙周膜间隙、牙骨形态和关节刚度（ΔS/Δage）随年龄的变化 SD、HD、RM组。RM将确定一个年龄范围，以优化纤维关节的保存。目的 2：评估适应性纤维关节随年龄增长的机械生物学过程。时空 在骨、牙骨质和牙骨质中的生物学表达（BE）（ΔBE/Δ年龄基因和基质蛋白）的变化 将绘制各年龄组的PDL附着点。差异表达基因与矿物形成 牙周膜附着点及牙周膜增宽、变窄区基质因子的吸收 组（SD、HD、RM）将被关联。目的3：评估拟定年龄范围对 实验性牙齿移动导致长期功能能力。结果 物理化学和生物学措施将与目标1和2相同，但对ETM组[10] 在目标1和目标2中提议的参考标准年龄范围之前、期间和之后。意图逆转 在ETM模型中的应变放大PDL-端点处的自然生物过程也将被研究。

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.