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

在我们以前的研究中，我们强调了考克斯-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，我们的工作假设是考克斯-2维持机械刺激的合成代谢作用，导致初始机械输入的放大。我们测试了考克斯-2无效，一岁大的小鼠受损的声波加速骨折修复，使其骨折的股骨进行机械刺激与LIPUS，低强度脉冲超声。由于10周龄的考克斯-2敲除小鼠（Dinchuk，1995）的股骨骨折愈合速度几乎与正常同窝出生小鼠相似，因此选择较年长的小鼠作为实验动物。另一方面，我们在一岁大的基因敲除小鼠的骨折股骨中观察到修复过程，这需要更长的时间，但LIPUS并没有显著加速。研究是否是由于考克斯-2相关的机械传导通路的阻断。下游靶分子如MMP-9、MMP-13和VEGF被认为是抑制机制所必需的。不仅软骨内骨形成中软骨的去除受到影响，而且未分化成骨细胞的发育也受到影响。考克斯-2在骨形成中的作用和非甾体抗炎药在老年患者骨折修复过程中可能出现的不良后果进行了讨论

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