Basic and clinical study aimed for the regenerative medicine of jaw bone by vibratory stimulation system

振动刺激系统颌骨再生医学的基础与临床研究

基本信息

批准号：
15390606
负责人：
KIMURA Hiroto
金额：
$ 6.46万
依托单位：
Hirosaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

Mechanical stress is thought to play an important role in bone remodeling, but the biological responses of human osteoblasts stimulated by mechanical stress are not well clarified. In oral maxillofacial region, the jaw bone defect after several types of surgery should be recovered by regenerated bone, however, there are no effective treatment methods available yet. In this research, we have developed new vibratory mechanism as like sound wave, that is clinically applicable source of mechanical stress, and designed research plan for bone regeneration. First, we clarifies the effect of vibratory stimulation on osteoblasts and/or fibroblasts, we investigated the production and/or the expression of COX-2,RANKL,OPG,Cbfa-1,BMP-4 and VEGF. Secondly, we carry out experiments on animals, adding vibratory stimulation on defect in the rat skull.Adding vibratory stimulation on cultured osteoblasts, the expression of COX-2 mRNA was significantly increased, otherwise the protein production was not increased. In cultured fibroblasts, the expression of VEGF mRNA was increased in time-dependent manner. However, the protein production and mRNA expression of RANKL,OPG, Cbfa-1,BMP-4 was not changed in osteoblasts and fibroblasts. In animal experiments, vibratory stimulation had no appreciable change in bone remodeling.We conclude that vibratory stimulation was cost-effective method as well as suitable for clinical application, however, it's effects on bone regeneration may be rather small compared to other mechanical stress loading methods. In the future, we intend to identify key molecule of bone remodeling from the results of cDNA microarray analysis performed in this study.

人们认为机械应力在骨骼重塑中起着重要作用，但是没有很好地阐明由机械应力刺激的人成骨细胞的生物学反应。在口腔上颌面区域，应通过再生骨骼回收几种类型的手术后的下颌骨缺损，但是，尚无有效的治疗方法。在这项研究中，我们开发了像声波一样的新振动机制，它是临床上适用的机械应力来源，并设计了用于骨再生的研究计划。首先，我们阐明了振动刺激对成骨细胞和/或成纤维细胞的影响，我们研究了COX-2，RANKL，OPG，CBFA-1，BMP-4和VEGF的产生和/或表达。其次，我们对动物进行实验，增加了大鼠头骨缺陷的振动刺激。添加对培养的成骨细胞的振动刺激，Cox-2 mRNA的表达显着增加，否则蛋白质的产生不会增加。在培养的成纤维细胞中，以时间依赖性方式增加了VEGF mRNA的表达。然而，在成骨细胞和成纤维细胞中，RANKL，OPG，CBFA-1，BMP-4的蛋白质产生和mRNA表达没有改变。在动物实验中，振动刺激没有明显变化的骨骼重塑。我们得出的结论是振动刺激是成本有效的方法，并且适合于临床应用，但是，与其他机械应力负荷方法相比，这对骨再生的影响可能很小。将来，我们打算从本研究中进行的cDNA微阵列分析的结果中鉴定出骨重塑的关键分子。