胫骨牵引成骨过程中骨形态形成蛋白4及其受体的表达  

Expression of bone morphogenetic protein 4 and its receptor in distraction osteogenesis of the tibia

作　　者：刘振东[1] 肖玉跃[1] 张朝跃[1] 陶建春[1] 黄祖发[1] 

机构地区：[1]中南大学湘雅三医院骨科,湖南省长沙市410013

出　　处：《中国组织工程研究与临床康复》2011年第20期3616-3620,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：湖南省自然科学基金项目"2型糖尿病对骨再生与修复的影响"资助(编号:05FJ3066)~~

摘　　要：背景:骨形态形成蛋白4及其受体在骨再生和修复过程中起着重要的作用,但具体机制尚不清楚。目的:建立小鼠胫骨牵引成骨模型,分析骨形态形成蛋白4及其受体在牵引成骨过程中的表达,探讨机械牵张力转化为生物信号从而调节骨再生过程的机制。方法:健康雄性8周龄CD-1小鼠36只,按照手术时间随机分成术后第5,9,13,17,24和31天组,每组6只。所有小鼠均接受左胫骨中上段低能截骨,安置体外延长固定架,截骨后5d为静止期;截骨后第6天起开始每天进行胫骨延长,速率为0.2mm,2次/d,共12d,为牵引期;自第18天停止牵引,为固塑期。于术后第5,9,13,17,24和31天分别处死动物,采集胫骨标本,作组织学检查、RT-PCR和原位杂交实验分析骨形态形成蛋白4及其受体激活素样激酶3以及骨钙素的表达。结果与结论:组织学检查显示静止期修复过程基本与骨折愈合过程相似。小鼠骨折断端在持续牵引下有明显的骨痂形成,骨形态形成蛋白4及其受体激活素样激酶3以及骨钙素的mRNA的表达明显增强。结果表明,牵引成骨是一种持续的骨再生过程,机械张力可通过刺激骨形态形成蛋白4及其受体以及骨钙素的持续高表达维持骨痂的不断形成和再塑,以充填连续延长的骨折间隙。BACKGROUND：Bone morphogenetic protein 4 （BMP-4） and its receptor play an important role in bone regeneration and repair process,but the mechanism is still unclear.OBJECTIVE：To understand how the mechanical forces are translated into biological signals that regulate bone regeneration and repair,we investigated the expression of BMP-4 and its receptor using a mouse tibia for distraction osteogenesis.METHODS：A total of 36 healthy male CD-1 mice of 8 weeks old,which were divided into six groups in the experiment,with 6 ones in each group.All animals received placement of the external fixator and osteotomy on the left tibia.Distraction protocol included 5 days latency,12 days distraction,and 14 days consolidation.Distraction rate was 0.2 mm,twice a day.The animals were sacrificed at 5,9,13,17,24,and 31 days after the operation.The lengthened tibiae were harvested and distraction gaps were analyzed by histology,and the expression of BMP-4 and its receptor and osteocalcin was evaluated by using reverse transcription-polymerase chain reaction （RT-PCR） and in situ hybridization.RESULTS AND CONCLUSION：Histological analysis demonstrated that the healing process of osteotomic gap was similar to fracture repair in the latency.RT-PCR and in situ hybridization analysis showed that expression of BMP-4 and its receptor were higher in distraction compared with in latency.The findings from this study suggested that distraction osteogenesis is a unique form of bone regeneration.The mechanic forces induce expression of local growth factors and receptors （such as BMP-4 and ALK-3） that maintain callus formation and remodelling which fill osteotomic gap gradually enlarged by mechanical forces.

关 键 词：机械张力 牵引成骨 骨再生 骨形态形成蛋白4 激活素样激酶3 

分 类 号：R318[医药卫生—生物医学工程]