RANKL/OPG信号通路在PTH促进SFA正颌外科术后颌骨改建和正畸加速中的调控效应研究

项目名称： RANKL/OPG信号通路在PTH促进SFA正颌外科术后颌骨改建和正畸加速中的调控效应研究

项目编号： No.81460101

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 唐正龙

作者单位： 贵州医科大学

项目金额： 47万元

中文摘要： 以手术优先（Surgery-first approach，SFA）的正颌外科-正畸联合治疗以及应用甲状旁腺素（parathyroid hormone, PTH）加速牙颌面畸形术后正畸牙移动的机制尚不清楚。课题组前期研究发现RANKL/OPG信号通路在PTH调控骨转换水平而加速骨改建过程中起重要作用。本研究通过建立兔第一磨牙正畸矫治模型和上下颌骨正颌外科手术模型，术后持续性或间隙性给予不同剂量的PTH。研究SFA正颌外科对正畸牙移动速度的影响、正畸牙张力侧和压力侧破骨细胞活化和牙槽骨组织形态学改变、骨转换生化标志物水平检测，以及RANKL/OPG信号通路中关键分子信号的表达效应。探索SFA正颌外科加速正畸牙移动和颌骨改建的调控机制，PTH能否进一步加速正颌外科术后正畸牙移动及其效应机制，筛选适宜的PTH给药方式和剂量。为推广SFA正颌外科并应用PTH缩短骨性牙颌面畸形疗程提供理论和实验依据。

中文关键词： 骨改建；正颌外科；甲状旁腺素；信号通路；正畸牙移动

英文摘要： In recent years, the prospect of surgery-first approach (SFA) in surgical-orthodontic treatment of skeletal malocclusion and the administration of parathyroid hormone (PTH) to facilitate orthodontics and bone remodeling have attracted the close attention of researchers. However, the mechanisms of SFA orthognathic surgery and PTH in accelerating tooth movement and bone remodeling have not been elucidated.Our previous study showed that the RANKL/OPG signaling pathway played an important role on the bone turn over and bone remodeling process through the intermitent administration of PTH in a rabbit mandibular defect model. In this study, a rabbit model of first molar orthodontics and bi-maxillary orthognathic surgery will be established. After the bi-maxillary orthognathic surgery, the upper and lower first premolars will mesially tracted with a traction force of 80cN, and the intermittent or continuous administration of PTH will be administrated through subcutaneous injection. During the orthodontics process, the orthodontic tooth mobility will be analysed, and bone remodeling will be assessed through histomorphological and morphometric analysis of alveolar bone tissue, serum levels of bone turnover detection, tartrate-resistant acid phosphatase (TRAP) staining positive osteoclasts number calculation and osteoclastogenic activity analysis at the orthodontic compression and tension sites. In addition, the molecular expression and transcription in RANKL/OPG signaling system,which plays an important role between bone remodeling and tooth movemnt, will be detected through PCR, Western blotting, ELISA and IHC analysis. The purpose of this study is to examine the feasibility of using PTH and SFA orthognathic surgery to promote the tooth movement and bone remodeling, and to titrate the optimal mode and dosage of PTH in accelerating tooth movement during orthognathic surgery, and to provide a preliminary investigation of the underlying mechanisms of this phenomenon. The specific aims of the study are provide theoretical support and an experimental basis for the clinical application of PTH and SFA orthognathic surgery in accelerating the tooth movement and shortening the entire treatment period in skeletal dento-facial deformities.

英文关键词： bone remodeling;orthognathic surgery;parathyroid hormone;signal pathway;tooth movement