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Mechanisms of anabolic action in low intensity pulsed ultrasound-accelerated fracture repair -synergistic effect on stretch-loading -

低强度脉冲超声加速骨折修复中的合成代谢作用机制-拉伸加载的协同效应-

基本信息

批准号：
14571409
负责人：
MIKUNI-TAKAGAKI Yuko
金额：
$ 2.5万
依托单位：
Kanagawa Dental College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

In our previous studies, we emphasized the role of COX-2 as an amplifier of mechanical response of primary and established bone cells. With that in mind, our working hypothesis was that COX-2 sustains the anabolic effect of mechanical stimuli resulting in the amplification of the initial mechanical input. We tested COX-2 null, one-year-old mice for impaired sonic accelerated fracture repair by subjecting their fractured femur to mechanical stimulation with LIPUS, low-intensity pulsed ultrasound. Choice of older mice for experimental animals was made since the fractured femur in the COX-2 knockout mice (Dinchuk, 1995) of 10 weeks of age, healed at an almost similar rate to those in normal littermates. On the other hands, we have observed the repair process, which took much longer, was not significantly accelerated by LIPUS, in the fractured femur of one-year-old knockout mice. Whether it is due t the blockade of COX-2-related mechanotransduction pathways was investigated. Downstream target molecules such as MMP-9, MMP-13 and VEGF are suggested to be essential to the inhibitory mechanism. Not only the cartilage removal in endochondral bone formation, but the development of undifferentiated osteogenic cells are affected. Both the role of COX-2 in bone formation and the possible undesirable outcome of NSAIDs use in elderly patients during the fracture repair are discussed

在我们以前的研究中，我们强调了COX-2作为原代和已建立的骨细胞机械反应的放大器的作用。考虑到这一点，我们的工作假设是COX-2维持机械刺激的合成代谢效应，导致初始机械输入的放大。我们测试了COX-2基因缺失的一岁小鼠，通过用LIPUS低强度脉冲超声波对其骨折的股骨进行机械刺激，进行了受损的声波加速骨折修复。选择年长的小鼠作为实验动物是因为10周龄的COX-2基因敲除小鼠(Dinchuk，1995)的股骨骨折，愈合速度几乎与正常小鼠相似。另一方面，我们观察到，在一岁大的基因敲除小鼠的股骨骨折中，LIPUS并没有显著加速修复过程，修复过程花费的时间要长得多。探讨是否由于COX-2相关的机械转导通路受阻所致。下游靶分子如基质金属蛋白酶-9、基质金属蛋白酶-13和血管内皮生长因子被认为是抑制机制所必需的。不仅影响软骨内成骨过程中软骨的去除，而且影响未分化成骨细胞的发育。我们讨论了环氧合酶-2在骨形成中的作用以及在老年患者骨折修复期间使用非类固醇抗炎药可能产生的不良后果。