Chikazu D, Tomizuka K, Ogasawara T, Saijo H, Koizumi T, Mori Y, Yonehara Y, Susami T, Takato T
Department of Oral-Maxillofacial Surgery, Dentistry and Orthodontics, The University of Tokyo Hospital, Bunkyo, Tokyo, Japan.
Int J Oral Maxillofac Surg. 2007 May;36(5):441-6. doi: 10.1016/j.ijom.2006.11.011. Epub 2007 Mar 21.
The aim of this study was to examine the effect of cyclooxygenase (COX)-2 on bone response after the placement of implants in the femurs of mice. titanium implants 1.0mm in diameter were placed into the middle of the femurs of 9-week-old male COX-2 wild-type (COX-2(+/+)) and knockout (COX-2(-/-)) mice. For RNA analysis, the mice were killed 0, 1, 2, 4, 7 and 56 days after implantation. RNA was extracted from the bone surrounding the implants. For histological analysis, the mice were killed 4 and 8 weeks after treatment, and undecalcified sections were prepared. Contact microradiography was performed, and the sections were stained with 1% toluidine blue for histological examination. Histomorphometric measurements were obtained with a computer-based image analyser to quantify bone newly formed around the implant and the rate of implant-bone contact. Expression of COX-2 and osteocalcin mRNA was induced in bone surrounding implants in COX-2(+/+) mice, but not in COX-2(-/-) mice. In cortical bone, the implant surface was in direct contact with newly formed bone lamellae in COX-2(+/+) mice; new bone formation was minimal in COX-2(-/-) mice. These results suggest that COX-2 plays an essential role in osseointegration and provide evidence that COX-2-selective non-steroidal anti-inflammatory drugs may interfere with osseointegration clinically.
本研究的目的是检测环氧化酶(COX)-2对小鼠股骨植入物植入后骨反应的影响。将直径1.0mm的钛植入物植入9周龄雄性COX-2野生型(COX-2(+/+))和基因敲除型(COX-2(-/-))小鼠的股骨中部。为进行RNA分析,在植入后0、1、2、4、7和56天处死小鼠,从植入物周围的骨组织中提取RNA。为进行组织学分析,在治疗后4周和8周处死小鼠,制备不脱钙切片。进行接触式显微放射摄影,切片用1%甲苯胺蓝染色以进行组织学检查。使用基于计算机的图像分析仪进行组织形态计量学测量,以量化植入物周围新形成的骨组织以及植入物与骨的接触率。COX-2(+/+)小鼠植入物周围的骨组织中诱导了COX-2和骨钙素mRNA的表达,而COX-2(-/-)小鼠中未诱导。在皮质骨中,COX-2(+/+)小鼠的植入物表面与新形成的骨板直接接触;COX-2(-/-)小鼠中的新骨形成极少。这些结果表明COX-2在骨整合中起重要作用,并提供了证据表明COX-2选择性非甾体抗炎药在临床上可能会干扰骨整合。