骨形态发生蛋白2表达异常与脊柱的融合

Abnormal expression of bone morphogenetic protein 2 and spinal fusion

目的:综述近几年来国内外对骨形态发生蛋白2表达异常及其基因突变的研究,重点分析突变对脊柱融合的影响,为基因重组骨移植提供理论依据。资料来源:应用计算机检索Medline和Science Direct Online数据库1989-01/2007-01期间与骨形态发生蛋白2表达异常及脊柱融合相关的文章,检索词为"BMP2,BMP,gene mutation,mutation,gene expression,abnormal expression,spinal fusion,bony fusion,bone transplantation",限定文章语言种类为English。同时计算机检索中国期刊全文数据库2000-01/2007-01期间与骨形态发生蛋白2表达异常及脊柱融合相关的文章,检索词为"骨形态发生蛋白2,脊柱融合,骨移植,基因突变,表达异常",限定文章语言种类为中文。资料选择:对资料进行初审,选择有关骨形态发生蛋白2生物学活性、信号转导机制、基因突变、与骨诱导的关系、在脊柱融合中的研究进展的文献,共收集到121篇,排除综述类及重复研究。资料提炼:选择其中有代表性的30篇进行综述,涉及到骨形态发生蛋白2的生物学活性、诱导成骨机制、突变的分子学基础、基因突变及影响蛋白表达异常的其他因素。资料综合:骨移植植骨融合的形成是一个多因子、多基因的过程,涉及到骨生成、骨诱导和骨传导3个环节。骨形态发生蛋白2是骨发育和修复的关键调节剂,骨折愈合时尤其需要。国内外学者对于骨形态发生蛋白2基因的自身突变研究取得了很大进展,已检测出不同部位多个位点的突变。基因变异导致所编码氨基酸发生改变,从而引起相应多肽结构发生变异,影响蛋白质的理化性质。无论是体内的骨形态发生蛋白2抑制因子,突变导致的生物活性改变,还是其增龄性效应,最终都将引起局部骨形态发生蛋白2含量下降及生物学活性减退,可能直接导致脊柱融合术后植骨愈合不良或植骨不愈合的发生。结论:对骨形态发生蛋白2表达异常尤其对其基因进行突变分析,寻找影响植骨融合的遗传学因素,具有非常重要的临床意义。

OBJECTIVE： To review the researches on the abnormal expression and gene mutation of bone morphogenetic protein 2 （BMP2） at home and abroad, and analyze the effect of BMP2 gene mutation on spinal fusion, so as to provide theory for genetic recombination of bone transplantation. DATA SOURCES： A computer-based online search of Medline and Science Direct was undertaken to identify the English articles about the relationship of BMP2 and spinal fusion dated between January 1989 and January 2007 with the keywords of ＂BMP2, BMP, gene mutation, mutation, gene expression, abnormal expression, spinal fusion, bony fusion, bone transplantation＂. Meanwhile, CNKI was searched for relevant Chinese articles published between January 2000 and January 2007 with the keywords of ＂BMP2, spinal fusion, bone transplantation, gene mutation, abnormal expression＂ in Chinese. STUDY SELECTION： The data were firstly selected, and only 121 articles which included the information about the biological activity of BMP2, the mechanism of signal transduction, gene mutation, relationship with bone induction and research progression in spinal fusion were selected. Repetitive studies and reviews were excluded. DATA EXTRACTION： Thirty typical articles were reviewed involving the biological activity of BMP2, the mechanism of bone induction, molecular foundation of mutation, gene mutation and other factors for abnormal expression of BMP2. DATA SYNTHESIS： The formation of bony fusion is a process of multi-factor and multi-gene, involving bone formation, bone induction and bone conduction. BMP2 is a critical moderator for bone development and repair, especially for bone healing. Tremendous progress in BMP2 gene mutation has been achieved by the scholars at home and abroad, and many different mutations have been detected. Genovariation leads to the alteration of coding amino acids and the variation of corresponding polypeptide structure, and then affects the physicochemical property of protein. BMP2 antagonists, changes of the biological activity caused by gene mutation, and aging effect could result in the decrease of local BMP2 contents and the breakdown of biological activity, which may directly cause poor even no bony fusion after spinal fusion. CONCLUSION： It is of great clinical significance to analyze the abnormal expression and gene mutation of BMP2 and search for the genetic factors of bony fusion.