Analysis of periodontal tissue remodeling mechanism induced by mechanical stress and the regulation by gene transfer

机械应力诱导牙周组织重塑机制及基因转移调控分析

基本信息

批准号：
16390602
负责人：
CHIBA Mirei
金额：
$ 9.57万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390602/
关键词：
Mechanical stress Periodontal tissue Gene transfer Orthodontic tooth movement Remodeling Periodontal ligament cells Osteoblasts Osteoclasts リモデリングエレクトロポレーション Bone Morphogenetic Protein 超音波血管新生因子アポトーシス骨吸収骨形成 OPG RANKL

项目摘要

The purpose of this research is to analyze the expression of molecules induced by the mechanical stress, and then to select the functional bone remodeling regulatory molecules, and to transfer these genes into the periodontal tissue, and finally, to control the local bone remodeling mechanism.1. The analysis of molecules induced by mechanical stress in the cells of the periodontal tissue(1) Both the osteoblasts differentiation-regulating factor and the osteoclast differentiation-regulating factor produced from the periodontal ligament (PDL) cells: Soluble factor produced from PDL cells stimulated by cyclic tension force inhibited osteoblast differentiation, suppressing the expression of transcription factor, osterix and runx-2. Osteoprotegerin (OPG) was also produced by PDL cells, and on the other hand, inhibited the osteoclast formation.(2) The differences of the response to continuous compression force between PDL cells and the osteoblasts: The PDL cells were resistance to the compre … More ssion force, and promoted the production of the angiogenesis factor corresponding to the compression force. On the other hand, osteoblasts were caused apoptosis by activation of caspase-3 via caspase-8 signaling pathway.2. Development of appropriate in vivo delivery system of in vivo gene transfer to periodontal tissue and functional analysis(1) Receptor activator of NF- r B ligand (RANKL) and the OPG gene transfer by the HVJ-envelop vector method: RANKL gene transfer promoted the experimental tooth movement (ETM). Moreover the OPG gene transfers inhibited ETM and relapse after ETM by regulating the osteoclast formation.(2) Bone morphogenetic protein (BMP) -4-gene transfer by the in vivo electroporation method: The alveolar bone density increased by the BMP-4 gene transfer, and the relapse after ETM inhibited.(3) The gene transfer by the ultrasound using nanobubbles together: Using the nanobubbles together, high efficiency and transient expression were observed in the experiment targeting to PDL cells in vitro, and to periodontal tissue in vivo. Less

本研究的目的是分析机械应力诱导的分子表达，进而选择功能性骨重塑调节分子，并将这些基因转移到牙周组织中，最终控制局部骨重塑机制。 1.牙周组织细胞机械应力诱导分子分析(1)牙周膜(PDL)细胞产生的成骨细胞分化调节因子和破骨细胞分化调节因子：可溶性因子循环张力刺激的 PDL 细胞产生的 OPG 抑制成骨细胞分化，抑制 PDL 细胞产生的转录因子 osterix 和 runx-2 的表达，另一方面抑制破骨细胞的形成。(2) ) PDL细胞与成骨细胞对持续压力反应的差异：PDL细胞对压力有抵抗力，并促进血管生成的产生另一方面，通过caspase-8信号通路激活caspase-3导致成骨细胞凋亡。2.开发适当的体内基因转移系统以进行牙周和组织功能分析（ 1)NF-rB配体受体激活剂(RANKL)和通过HVJ-包膜载体方法的OPG基因转移：RANKL基因转移促进实验性牙齿移动(ETM)。 OPG基因转移通过调节破骨细胞的形成抑制ETM和ETM后的复发。(2)通过体内电穿孔法进行骨形态发生蛋白(BMP)-4-基因转移：BMP-4基因转移增加了牙槽骨密度，并且(3)纳米气泡联合超声基因转移：纳米气泡联合使用，在靶向PDL细胞的实验中观察到高效率和瞬时表达。体外对牙周组织的影响较小。