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

在我们之前的研究中，我们强调了COX-2作为原代和成熟骨细胞机械反应放大器的作用。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无效的一岁小鼠，通过使用LIPUS（低强度脉冲超声）对其骨折的股骨进行机械刺激来检测受损的超声加速骨折修复。选择年龄较大的小鼠作为实验动物，是因为COX-2基因敲除小鼠（Dinchuk, 1995）在10周龄时股骨骨折，愈合速度与正常窝鼠几乎相似。另一方面，我们观察到，在一岁的基因敲除小鼠的股骨骨折中，修复过程需要更长的时间，LIPUS并没有显著加速修复过程。是否由于阻断cox -2相关的机械转导途径而引起。下游靶分子如MMP-9、MMP-13和VEGF被认为对抑制机制至关重要。软骨内成骨不仅影响软骨的去除，而且影响未分化成骨细胞的发育。本文讨论了COX-2在骨形成中的作用以及在骨折修复过程中使用非甾体抗炎药可能产生的不良后果

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