Cyclo-oxygenase 2 function is essential for bone fracture healing
Cyclo-oxygenase 2 function is essential for bone fracture healing
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DOI：
10.1359/jbmr.2002.17.6.963
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发表时间：
2002-06-01
影响因子：
6.2
通讯作者：
O'Connor, JP
中科院分区：
文献类型：
--
作者：
Simon, AM;Manigrasso, MB;O'Connor, JP
尽管胚胎骨发育和骨折愈合之间在分子和组织学上有相似之处，但炎症是骨折愈合的早期阶段，在发育期间不会发生。环氧合酶2（考克斯-2）在炎症部位被诱导并产生促炎性的胡萝卜素。为了确定考克斯-2是否在骨折愈合中起作用，用考克斯-2选择性非甾体抗炎药（NSAID）处理大鼠以停止考克斯-2依赖性前列腺素的产生。放射学、组织学和机械测试确定，用考克斯-2-选择性NSAID（塞来昔布和罗非昔布）治疗的大鼠骨折愈合失败。在考克斯-2基因无效突变纯合子小鼠中，正常骨折愈合也失败了。这表明考克斯-2活性是正常骨折愈合所必需的，并证实考克斯-2-选择性NSAID对骨折愈合的作用是由考克斯-2活性的抑制引起的，而不是由药物副作用引起的。组织学观察表明，考克斯-2是骨折愈合过程中正常软骨内骨化所必需的。由于缺乏COX 2的小鼠形成正常的骨骼，我们的观察表明，胎儿骨发育和骨折愈合是不同的，考克斯-2功能是骨折愈合特别重要。
Despite the molecular and histological similarities between fetal bone development and fracture healing, inflammation is an early phase of fracture healing that does not occur during development. Cyclo-oxygenase 2 (COX-2) is induced at inflammation sites and produces proinflammatory prostaglandins. To determine if COX-2 functions in fracture healing, rats were treated with COX-2-selective nonsteroidal anti-inflammatory drugs (NSAIDs) to stop COX-2-dependent prostaglandin production. Radiographic, histological, and mechanical testing determined that fracture healing failed in rats treated with COX-2-selective NSAIDs (celecoxib and rofecoxib). Normal fracture healing also failed in mice homozygous for a null mutation in the COX-2 gene. This shows that COX-2 activity is necessary for normal fracture healing and confirms that the effects of COX-2-selective NSAIDs on fracture healing is caused by inhibition of COX-2 activity and not from a drug side effect. Histological observations suggest that COX-2 is required for normal endochondral ossification during fracture healing. Because mice lacking Cox2 form normal skeletons, our observations indicate that fetal bone development and fracture healing are different and that COX-2 function is specifically essential for fracture healing.