重组人骨形成蛋白2对下颌骨牵引成骨中整合素β_1表达的影响

Effects of recombinant human bone morphogenetic protein 2 on integrin beta 1 expression during mandibular distraction

背景:骨组织中整合素表达水平可影响细胞功能,调控成骨和骨吸收,但整合素只有被其他因子激活后才能发挥强大的黏附作用,重组人骨形成蛋白2具有此作用吗?目的:观察不同质量重组人骨形成蛋白2对兔下颌骨牵引成骨区整合素β1的表达影响。设计、时间及地点:随机分组动物实验,组织学观察,于2006-05/2007-05在辽宁医学院动物实验中心和免疫组化中心完成。材料:日本成年大耳白兔45只。重组人骨形成蛋白2由北京军事医学科学院三所八室提供。方法:选用日本成年大耳白兔45只建立下颌骨牵引模型,造模后采用随机数表法将分为3组:空白对照组、1.5,3.0mg重组人骨形成蛋白2胶原海绵载体组,15只/组。分别将不含重组人骨形成蛋白2胶原海绵载体、含1.5,3.0mg重组人骨形成蛋白胶原复合物植入3组兔下颌骨切开处,固定、牵引0.4mm/次,2次/d,共计5d,总延长下颌骨4mm。主要观察指标:牵引后稳定期第1,3,7,14,28天取牵引区新生骨痂行免疫组织化学染色观察骨组织中整合素β1的表达。结果:45只日本大耳白兔均建模成功,进入结果分析。整合素β1在牵引区表达主要反映在牵引7d后。在同一时间内,随着重组人骨形成蛋白2质量的增加,整合素β1阳性细胞表达率、阳性面积百分比逐渐增多(P<0.05);在同一质量下,随着时间的延长,整合素β1阳性细胞阳性表达率、阳性面积百分比逐渐上升(P<0.05)。结论:局部应用外源性重组人骨形成蛋白2在牵引成骨中晚期对整合素β1的表达有促进作用,并且整合素β1的表达对重组人骨形成蛋白2呈质量依赖性。

BACKGROUND： Integrin levels can affect cellular function, regulate bone formation and bone resorption. However, this process need activated by other factors, whether recombinant human bone morphogenetic protein 2 （rhBMP-2） has this effect is poorly understood. OBJECTIVE： To study the effects of the different concentration of rhBMP-2 on the expression of inergrin β1 during the mandibular distraction in rabbits. DESIGN, TIME AND SETTING： The randomized, controlled, animal grouping experiment of histological observation was performed at the Animal Experimental Center and Immunohistochemistry Center of Liaoning Medical University from May 2006 to May 2007. MATERIALS： A total of 45 Japanese white rabbits were used. rhBMP-2 was supplied by Beijing Academy of Military Medical Sciences. METHODS： The rabbits were prepared for mandibular distraction models and randomly assigned into control, 1.5 mg rhBMP-2 and 3.0 mg rhBMP-2 groups, with 15 animals in each group. Collagen sponge and collagen binding proteins were implanted into mandibles of rabbits, respectively, and distraction 0.4 mm per time, twice per day for 5 days. The mandibles were lengthened 4 mm. MAIN OUTCOME MEASURES： The expression of integrin β1 was detected using immunohistochemistry at days 1, 3, 7, 14, and 28 after distraction. RESULTS： All rabbits were included in the final analysis. The integrin β1 mainly expressed at 7 days after distraction. At the same time point, when concentration rhBMP-2 was increased, the positive integrin β1 rate and positive stained area percentage were increased （P 〈 0.05）. Compared to the same concentration, the positive integrin β1 rate and positive stained area percentage were gradually increased as time prolonged （P 〈 0.05）. CONCLUSION： The integdn β1 expression can be promoted by rhBMP-2 at the anaphase of mandibular distraction osteogenesis in a concentration-dependent manner.