Role of Angiogenesis During Distraction Osteogenesis

血管生成在牵张成骨过程中的作用

基本信息

批准号：
6766925
负责人：
ROBERTO S CARVALHO
金额：
$ 8.08万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-07-01 至 2005-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The treatment and correction of dentoalveolar malocclusions and osseous craniofacial abnormalities is based primarily on the application of mechanically-generated forces. During orthodontic and ortho-surgical treatments, mechanical transport is routinely used for the correction of tooth position within the bone and for expansion of palatal width to accommodate new tooth growth and discrepancies in jaw length. The latter form of bone induction and remodeling is nearly identical to those found in classical applications of distraction osteogenesis used for limb lengthening. While these procedures are extensively used clinically, the basic mechanisms by which they promote new bone formation are not well understood. One of the primary features of these procedures that generate bone by distraction is that they are primarily intramembranous processes devoid of extensive amounts of cartilage. An observed histological feature of these processes of bone regeneration is the observation of robust vascularization of the repair tissue both proceeding and continuing to be present during the regeneration process. The hypothesis of this proposal is that bone regeneration during distraction osteogenesis is driven by signals derived from the angiogenic process. In order to test this hypothesis and develop genetic models to examine the molecular mechanisms that regulate bone formation we have developed a murine model of distraction osteogenesis. In initial studies we will define the temporal and spatial expression of the angiogenic and bone morphogenetic signals that drive new bone formation during distraction osteogenesis. In subsequent experiments we will specifically block VEGF mediated angiogenesis using blocking antibodies to this angiogenic factor, and functionally test if this gene is a primary mediator of angiogenesis during distraction osteogenesis and if blocking its activity effects ossification. These experiments represent the first steps in defining the molecular mechanisms that regulate bone formation during distraction osteogenesis and test the functional role of angiogenic regulators in this process.

描述（由申请人提供）：牙槽咬合不正和骨性颅面畸形的治疗和矫正主要基于机械产生的力的应用。在正畸和正畸手术治疗期间，机械运输通常用于矫正牙齿在骨内的位置以及扩大腭宽度以适应新牙齿的生长和颌长度的差异。骨诱导和重塑的后一种形式几乎与用于肢体延长的牵引成骨的经典应用中发现的相同。虽然这些手术在临床上广泛使用，但它们促进新骨形成的基本机制尚不清楚。这些通过牵引产生骨的手术的主要特征之一是它们主要是膜内过程，缺乏大量软骨。这些骨再生过程的观察到的组织学特征是观察到修复组织的强血管化在再生过程中进行并继续存在。该提议的假设是，牵引成骨过程中的骨再生是由血管生成过程产生的信号驱动的。为了检验这一假设并开发遗传模型来检查调节骨形成的分子机制，我们开发了一种牵张成骨的小鼠模型。在初步研究中，我们将定义在牵引成骨过程中驱动新骨形成的血管生成和骨形态发生信号的时间和空间表达。在后续实验中，我们将使用该血管生成因子的阻断抗体特异性阻断 VEGF 介导的血管生成，并功能测试该基因是否是牵引成骨过程中血管生成的主要介质，以及阻断其活性是否会影响骨化。这些实验代表了定义牵引成骨过程中调节骨形成的分子机制的第一步，并测试了血管生成调节剂在此过程中的功能作用。