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Application of Mechanical Vibration to Enhance Orthodontic Tooth Movement

应用机械振动增强正畸牙齿移动

基本信息

批准号：
8269967
负责人：
Dawei Liu
金额：
$ 11.29万
依托单位：
MARQUETTE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-06-01 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8269967
关键词：
Adverse effects Affect Animals Anterior Appearance Blood Vessels Bone Resorption C57BL/6 Mouse Calculi Caring Cerebral Decortication Clinic Clinical Clinical Research Data Decalcification Dental Dental Cementum Dental Enamel Dental Hygiene Dinoprostone Face Frequencies Goals Grant Herb Human Injection of therapeutic agent Kale - dietary Knowledge Ligands Light Maxilla Mechanics Medical Metabolic Methods Modeling Motion Mus Nature Operative Surgical Procedures Oral Orthodontic Orthodontics Orthopedics Osteogenesis Patients Periodontal Ligament Periodontium Phase Physiological Plant Roots Procedures Process Production Proteins Rattus Reporting Research Role Root Resorption Scanning Side Signal Pathway Signal Transduction Solutions Staining method Stains Surface System Technology Testing Time Tissues Tooth Movement Tooth Socket Tooth structure Translating United States National Institutes of Health Vitamin D Weight-Bearing state Work alveolar bone base bone clinical application compliance behavior improved innovation insight mouse model prevent receptor activator of NF-kappa B response tool vibration

项目摘要

DESCRIPTION (provided by applicant): One of the key challenges in orthodontics is the long treatment time necessary to achieve adequate results. Developing solutions to this challenge would have a positive impact on the quality of orthodontic care. In an attempt to move teeth faster, two strategies had been explored, namely local injections of biomolecules such as PGE2 and RANKL, and surgical severance (decortication) of the alveolar bone. However, both methods have failed to be translated to clinical application because of their invasiveness. The long-term goal of this project is to apply mechanical vibration (MV) to enhance tooth movement in orthodontic patients to shorten overall treatment time. The overall objective of this project is to use a mouse model to better understand the effect of MV on orthodontic tooth movement (OTM) and to determine its effect on alveolar bone modeling as the underlying mechanism of this effect. OTM is a process of mechanically-induced modeling of periodontium wherein bone is resorbed on the compression side and formed on the tension side of the periodontal ligament (PDL). No matter how "light" a force is, due to the irregular surfaces of the dental root and alveolar socket wall, the blood vessels in the PDL are occluded to some extent, inducing a tissue damage called "hyalinization" and leading to a lag phase of OTM. Thus, increasing tooth motion without blood vessel blockage is the key to move teeth faster. One of the possible means of achieving this is to use MV to modify static orthodontic forces. Recently, resonance vibration has been shown to be able to increase OTM rate in rats (Nishimura, 2008). The mechanism leading to the effect, however, is not known. Our preliminary data in mice suggest increased OTM with MV. Based on these findings, we hypothesize that MV may be a powerful and non-invasive tool to enhance OTM and that the mechanism of this effect may be through the modulation of the OPG/RANKL and SOST signaling pathways. To test our hypotheses, we plan to complete the following specific aims (SA). SA1: To determine the effects of MV at physiological frequency on OTM rates. To target this specific aim, we will apply MV to the orthodontically moved maxillary 1st molars in mice every 3 days for 28 consecutive days. To quantify the rate of OTM, weekly radiographs and a microCT scan on the 28th day will be taken. Our working hypothesis is that MV enhances OTM rates. SA2: To prove that MV affects OTM by altering the modeling rates of the alveolar bone. To target this specific aim, undecalcified tissues will be sectioned to evaluate the histomorphometric parameters as well as histological staining. To gain insights into the mechanism, the production profile of three key bone metabolic regulatory molecules - OPG, RANKL and SOST proteins will be examined Immunohistochemically. Our working hypothesis is that MV increases bone resorption at the compression side of PDL by increasing the ratio of RANKL/OPG and the production of SOST protein. If our hypotheses prove to be correct, the logical next step will be to further investigate the mechanism of this phenomenon as well as to translate the current findings from animals to human clinical studies.

描述（由申请人提供）：治疗的关键挑战之一是达到足够结果所需的长治疗时间。开发解决这一挑战的方案将对正畸护理质量产生积极影响。为了更快地移动牙齿，已经探索了两种策略，即局部注射生物分子如PGE 2和RANKL，以及牙槽骨的手术切断（去皮质）。然而，这两种方法都未能转化为临床应用，因为它们的侵入性。本计画的长期目标是应用机械振动（MV）来促进正畸患者的牙齿移动，以缩短整体治疗时间。该项目的总体目标是使用小鼠模型，以更好地了解MV对正畸牙齿移动（OTM）的影响，并确定其对牙槽骨建模的影响，作为这种影响的潜在机制。OTM是一种机械诱导的牙周组织建模过程，其中骨在牙周膜（PDL）的压缩侧被吸收，并在张力侧形成。无论多么“轻”的力，由于牙根和牙槽窝壁的不规则表面，PDL中的血管在一定程度上被闭塞，诱导称为“玻璃化”的组织损伤，并导致OTM的滞后期。因此，在不堵塞血管的情况下增加牙齿运动是更快移动牙齿的关键。实现这一目标的一种可能方法是使用MV来修改静态正畸力。最近，共振已被证明能够增加大鼠的OTM率（Nishimura，2008）。然而，导致这种效应的机制尚不清楚。我们在小鼠中的初步数据表明MV增加了OTM。基于这些发现，我们假设MV可能是增强OTM的强大且非侵入性的工具，并且这种作用的机制可能是通过调节OPG/RANKL和SOST信号通路。为了验证我们的假设，我们计划完成以下具体目标（SA）。SA 1：确定生理频率下MV对OTM率的影响。为了实现这一特定目标，我们将每3天将MV应用于小鼠中移动的上颌第一磨牙，连续28天。为了量化OTM的发生率，将在第28天进行每周X线片和microCT扫描。我们的工作假设是，MV提高OTM率。SA 2：证明MV通过改变牙槽骨的建模率来影响OTM。为了实现这一特定目标，将对未脱钙组织进行切片，以评价组织形态学参数以及组织学染色。为了深入了解该机制，将通过免疫组织化学方法检查三种关键骨代谢调节分子- OPG、RANKL和SOST蛋白的产生概况。我们的工作假设是，MV通过增加RANKL/OPG的比例和SOST蛋白的产生来增加PDL压缩侧的骨吸收。如果我们的假设被证明是正确的，那么合乎逻辑的下一步将是进一步研究这种现象的机制，并将目前的研究结果从动物转化为人类临床研究。