Cyclooxygenase-2 inhibitor reduces simvastatin-induced bone morphogenetic protein-2 and bone formation in vivo

被引:27
|
作者
Bradley, J. D.
Cleverly, D. G.
Burns, A. M.
Helm, N. B.
Schmid, M. J.
Marx, D. B.
Cullen, D. M.
Reinhardt, R. A.
机构
[1] Univ Nebraska, Med Ctr, Coll Dent, Dept Surg Special, Lincoln, NE 68583 USA
[2] Univ Nebraska, Med Ctr, Coll Dent, Dept Oral Biol, Lincoln, NE 68583 USA
[3] Univ Nebraska, Dept Biometry, Lincoln, NE 68583 USA
[4] Creighton Univ, Osteoporosis Res Ctr, Omaha, NE 68178 USA
关键词
bone formation rate; bone morphogenetic protein-2; cyclooxygenase-2; simvastatin;
D O I
10.1111/j.1600-0765.2006.00943.x
中图分类号
R78 [口腔科学];
学科分类号
1003 ;
摘要
Simvastatin, a cholesterol-lowering drug, also stimulates oral bone growth when applied topically, without systemic side-effects. However, the mechanisms involved in vivo are not known. We hypothesized that bone morphogenetic protein-2, nitric oxide synthase, and cyclooxygenase-2 are involved, based on prior in vitro evidence. A rat bilateral mandible model, where 0.5 mg of simvastatin in methylcellulose gel was placed on one side and gel alone on the other, was used to quantify nitric oxide, cyclooxygenase-2 and bone morphogenetic protein-2 (via tissue extraction, enzyme activity or immunoassay), and to analyze the bone formation rate (via undecalcified histomorphometry). Cyclooxygenase-2 and nitric oxide synthase inhibitors (NS-398 and L-NAME, respectively) were administered intraperitoneally. Simvastatin was found to stimulate local bone morphogenetic protein-2, nitric oxide and the regional bone formation rate (p < 0.05), whereas NS-398 inhibited bone morphogenetic protein-2 and reduced the bone formation rate (p < 0.05). These data suggest an association between simvastatin-induced bone morphogenetic protein-2 and bone formation in the mandibular microenvironment, and the negative effect of cyclooxygenase-2 inhibitors on bone growth.
引用
收藏
页码:267 / 273
页数:7
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