BMP-4和BMP-6在小鼠胫骨牵引成骨过程中的表达  

The Expression of BMP-4 and BMP-6 in Distraction Osteogenesis of Mouse Tibia

作　　者：刘振东[1] 张朝跃[1] 詹瑞森[1] 张迪华[1] 臧晓方[1] 江皓[1] 吴松[1] 

机构地区：[1]中南大学湘雅三医院骨科,中国湖南长沙410013

出　　处：《实用预防医学》2004年第4期743-746,共4页Practical Preventive Medicine

摘　　要：目的　应用小鼠胫骨牵引成骨模型 ,分析骨形态形成蛋白 (BoneMorphogeneticprotein ,BMP)在牵引成骨过程中的表达 ,探讨机械牵张力怎样转化成为生物信号以调控骨再生过程。　方法　本研究采用 8周龄雄性CD— 1小鼠3 6只 ,所有小鼠接受左胫骨中上段骨干横行截骨 ,安置特制延长外固定架 ,胫骨牵引过程包括 5d静止期 ,12d牵引期和70d固塑期 ,牵引速率为 0 .1mm /Bid ,共 0 .2mm/d。术后于不同时间点分组杀取动物 ,采集左胫骨标本 ,分别作组织学检查 ,RT—PCR和免疫组织化学检测。　结果　组织学检查显示静止期其修复过程基本与骨折愈合相似。牵引期 ,被牵引骨痂显示三个典型的生物学功能区 :纤维间区 ,初始骨基质前沿和微脊柱形成区。固塑期早期 ,牵引骨痂骨性愈合 ,第 10周骨髓腔再通 ,新生骨再塑基本上完成。RT -PCR分析显示机械牵张力能提高BMP -4和BMP -6的表达 ,而BMP -7仅在牵引期后期和固塑期早期微弱表达。免疫生化检测表明BMP -4在肥大软骨细胞和成熟的骨细胞中表达 ,而BMP -6在早期软骨细胞和成骨细胞中表达。　结论　我们的实验结果显示牵引成骨是一种持续的骨再生过程 ,机械张力通过刺激局部生长因子 (如BMP -4和BMP -6)的持续表达 ,维持骨痂的不断形成和再塑 ,以填充被逐渐延长的骨间隙。objective To understand how the mechanical forces are translated into biological signals that regulate bone regeneration and repair,we investigated the expression of Bone Morphogenetic proteins (BMPs) using a mouse tibia for distraction osteogenesis. Methods Thirty-six male CD-1 mice,8 weeks old,were used in the study. All animals received placement of the external fixators and osteotomy on the left tibia. Distraction protocol included 5 days latency,12 days distraction,and 70 days consolidation. Distraction rate was 0.2 mm/day. The animals were sacrificed at different time points postoperatively. The lengthened tibiae were harvested and distraction gaps were analyzed by histology,RT-PCR,and immunohistochemistry. Results Histological analysis demonstrated that the healing process of osteotomic gap was similar to fracture repair in the latency. The distraction callus consisted of fibrous interzone,primary matrix front,and microcolumn formation during the distraction. In the early stage of consolidation the distraction gap was bridged by bony callus. The newly formed bone was remodeled and medullary canal formed by 10 weeks of the consolidation. RT-PCR analysis showed that mechanical forces enhanced expression of BMP-4 and BMP-6. BMP-7 was weakly expressed. Immunohistochemical analysis demonstrated that BMP-4 was expressed by hypertrophic chondrocytes and osteocytes. BMP-6 was expressed by chondrocytes and osteoblasts. Conclusion Our data suggested that distraction osteogenesis is a unique form of bone regeneration. The mechanic forces induce expression of local growth factors that maintain callus formation and remodelling which fill osteotomic gap gradually enlarged by mechanical forces.

关 键 词：骨形态形成蛋白 机械张力 牵引成骨 骨再生 小鼠 

分 类 号：R68[医药卫生—骨科学]