Cyclo-oxygenase 2 function is essential for bone fracture healing

被引:426
作者
Simon, AM
Manigrasso, MB
O'Connor, JP
机构
[1] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Orthopaed, Newark, NJ 07103 USA
[2] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08855 USA
[3] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA
关键词
cyclo-oxygenase; 2; fracture healing; endochondral ossification; nonsteroidal anti-inflammatory drug; prostaglandin;
D O I
10.1359/jbmr.2002.17.6.963
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:963 / 976
页数:14
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