先天性胫骨假关节骨膜组织中基质金属蛋白酶对骨生成的影响*☆
李叔强1，扬 帆2，张 新1，王 萍3
课题背景：①先天性胫骨假关节是一种先天性的胫骨骨不连。有关它的病因和病理不完全清楚，治疗方法多，但效果不佳，复发率高，致残率高，40%左右的患者虽经多次手术但仍难逃截肢的厄运，是骨科界公认的一个难题。有关先天性胫骨假关节免疫组织化学、分子生物学及染色体方面的研究少有报道。②骨改建是一个复杂的多步骤过程，破骨细胞和成骨细胞的作用最为关键。而成骨细胞和破骨细胞不仅依赖基质金属蛋白酶对骨基质成分的直接降解，而且需要基质金属蛋白酶参与介导成骨细胞对成熟破骨细胞的活化以及破骨细胞的迁移和贴附等过程。
应用要点：本组结果发现假关节病变部位骨膜基质金属蛋白酶2和基质金属蛋白酶9表达量与创伤后骨折断端的骨膜相似，都高于正常骨膜，二者表达程度正相关性。说明在病理状态下基质内基质金属蛋白酶2和基质金属蛋白酶9活性增强，水解基质内胶原，在骨重建过程中骨的降解加快，加速骨吸收，导致骨吸收及骨生成失衡，是假关节不愈合的重要原因，为假关节的治疗提出了理论基础。
同行评价：正如其他许多先天性疾病的发病基础研究一样，先天性胫骨假关节的详细发病原因尚无统一的认识。了解基质金属蛋白酶2和基质金属蛋白酶9在先天性胫骨假关节中的作用和表达情况，可能对深入研究其作用机制具有一定的意义。
摘要
目的：基质金属蛋白酶在骨胚胎发育、改建及病理过程中所起的关键作用已引起人们的重视。明确基质金属蛋白酶2和基质金属蛋白酶9在先天性胫骨假关节病变处骨膜组织中的含量，探讨其与发病机制的关系。
方法：标本来自1990-01/2004-12年吉林大学第一临床医院骨关节二科收治的先天性胫骨假关节患者19例，年龄4~13岁，取材部位为假关节病变处骨膜组织；以10例正常骨膜做阴性对照，年龄10~15岁；15例胫骨闭合骨折断端周围骨膜做阳性对照。所取标本均经家属及本人同意。采用免疫组织化学方法观察上述标本骨膜组织内基质金属蛋白酶2和基质金属蛋白酶9表达。
结果：①基质金属蛋白酶2和基质金属蛋白酶9主要在血管内皮细胞胞浆中表达。②基质金属蛋白酶2和基质金属蛋白酶9在假关节病变骨膜内表达的阳性程度与创伤后骨折断端骨膜无明显差异（P > 0.05），但都明显高于正常骨膜（P < 0.05，P < 0.01）；二者在骨膜内的表达水平具有明显相关性（P < 0.01）。
结论：先天性胫骨假关节骨膜组织中基质内基质金属蛋白酶2和基质金属蛋白酶9在病理条件下表达增强影响骨生成，是形成假关节的重要原因。
关键词：胫骨/畸形；基质金属蛋白酶类；免疫组织化学；组织构建
李叔强，扬帆，张新，王萍.先天性胫骨假关节骨膜组织中基质金属蛋白酶对骨生成的影响[J].中国组织工程研究与临床康复，2008，12(2):213-216 [www.zglckf.com/zglckf/ejournal/upfiles/08-2/2k-213(ps).pdf]
1吉林大学第一临床医院骨关节二科，吉林省长春市 130021； 2榆树市医院骨科，吉林省榆树市 130400；3吉林大学第一医院耳鼻咽喉学－头颈外科，吉林省长春市 130021
李叔强☆，男，1973年生,吉林省长春市人，汉族，讲师，吉林大学在读博士，主要从事骨科创伤及人工关节的基础及临床研究。
shuqiangli3@
hotmail.com
通讯作者：王 萍，博士，副教授，吉林大学第一医院耳鼻咽喉－头颈外科，吉林省长春市 130021
吉林省科技厅科技发展计划资助课题（990567-1）*�������
中图分类号:R329.4
文献标识码:A
文章编号:1673-8225
(2008)02-00213-04
收稿日期：2007-03-10
修回日期：2007-09-28
(07-50-3-1390/W·Q)
Influence of matrix metalloproteinase on osteogenesis in the tibial periosteum of congenital pseudarthrosis
Abstract
AIM：We have paid more attentions on matrix metalloproteinase that has great roles in bone embryonic development, reestablishment and pathological process. This article defines the levels of matrix metalloproteinase-2 and matrix metalloproteinase-9 in periosteum of the congenital pseudarthrosis of tibia, and elucidate the pathogenesis.
METHODS: The periosteum of the tibia of 19 patients aged 4-13 years with congenital pseudarthrosis were studied at Second Department of Bone and Joint, First Clinical Hospital, Jilin University from January 1990 to December 2004. Ten normal periosteum from the healing site after tibia fracture of subjects aged 10–15 years and fifteen fresh periosteum from the close tibia fracture were taken as negative group and positive group. The subjects and their family members signed an informed consent. The expressions of matrix metalloproteinase-2 and matrix metalloproteinase-9 were determined by immunohistochemical method.
RESULTS: ①Matrix metalloproteinase-2 and matrix metalloproteinase-9 were found in vascular endothelial kytoplasm of pseudarthrosis. ②The levels of matrix metalloproteinase-2 and matrix metalloproteinase-9 on the congenital pseudarthrosis of tibia were similar to the periosteum of broken ends of the fractured bone (P > 0.05), but significantly higher than the normal periosteum（P < 0.05, P < 0.01）. The levels of matrix metalloproteinase-2 and matrix metalloproteinase-9 on periosteum had significant correlation（P < 0.01）.
CONCLUSION: The higher levels of matrix metalloproteinase-2 and matrix metalloproteinase-9 on periosteum leads bone building slowly and may be the reason related to the congenital pseudarthrosis of tibia.
Li SQ, Yang F, Zhang X, Wang P.Influence of matrix metalloproteinase on osteogenesis in the tibial periosteum of congenital pseudarthrosis.Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2008;12(2):213-216(China)
[www.zglckf.com/zglckf/ejournal/upfiles/08-2/2k-213(ps).pdf]
1Second Department of Bone and Joint, First Clinical Hospital, Jilin University, Changchun 130021, Jilin Province, China; 2Department of Orthopaedics, Yushu Hospital, Yushu 130400, Jilin Province, China; 3Department of Otolaryngology-Head and Neck, First Hospital, Jilin University, Changchun 130021, Jilin Province, China
Li Shu-qiang☆, Studying for doctorate, Lecturer, Second Department of Bone and Joint, First Clinical Hospital, Jilin University, Changchun 130021, Jilin Province, China
shuqiangli3@
hotmail.com
Correspondence to: Wang Ping, Doctor, Associate professor, Department of Otolaryngology-Head and Neck, First Hospital, Jilin University, Changchun 130021, Jilin Province, China
Supported by: the Technology Development Foundation of Science Department of Jilin Province, No. 990567-1*
Received: 2007-03-10
Accepted: 2007-09-28
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