获得性异位骨化的分子生物学机制  

Molecular biological mechanism of acquired heterotopic ossification

作　　者：熊洋[1] 周世博 俞兴[1] 毕连涌[1] 杨济洲[1] 王逢贤[1] 曲弋[1] 杨永栋[1] 赵丁岩 赵赫[1] 仇子叶 姜国正 Xiong Yang;Zhou Shibo;Yu Xing;Bi Lianyong;Yang Jizhou;Wang Fengxian;Qu Yi;Yang Yongdong;Zhao Dingyan;Zhao He;Qiu Ziye;Jiang Guozheng(Department of Orthopedics,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]北京中医药大学东直门医院骨科,北京市100700

出　　处：《中国组织工程研究》2024年第30期4881-4888,共8页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目(81973882),项目负责人:俞兴;国家自然科学基金项目(82305273),项目负责人:熊洋;北京中医药大学新教师启动基金项目(2023-BUCMXJKY007),项目负责人:熊洋。

摘　　要：背景:异位骨化是一个动态发展的过程,临床中不同亚型的异位骨化具有不同病因或诱导因素,但在异位骨化中后期进展阶段又表现出相似的病理过程,其中由于创伤等因素引起的获得性异位骨化具有较高的发病率。目的:对近年获得性异位骨化发生发展相关分子生物学机制研究进行综述。方法:以“分子生物学,异位骨化,机制”为检索词在中国知网、万方医学数据库进行检索,以“molecular biological,heterotopic ossification,mechanisms”为检索词分别在PubMed、Embase、Web of Science及Google Scholar数据库进行检索,检索时限为2016年1月至2022年8月,并根据获得文献进行补充检索,对所得文献进行筛选,最终纳入131篇文献进行综述分析。结果与结论:①获得性异位骨化的发生和发展是一个动态的过程,具有一定的隐匿性,因此该疾病的诊疗有一定的困难。②文章通过综述国内外相关文献,发现获得性异位骨化涉及骨形态发生蛋白、转化生长因子β、Hedgehog、Wnt及mTOR共5条主要信号通路,同时在局部微环境中涉及到Runx2、血管内皮生长因子、缺氧诱导因子、成纤维细胞生长因子及Sox9共5项核心枢纽因子,核心机制可能是不同信号通路之间的相互作用,影响机体成骨细胞前体细胞、成骨细胞微环境以及与此相关的细胞因子,进而影响机体骨代谢并导致获得性异位骨化的发生。③未来可以以异位骨化相关单细胞的成骨内稳态为研究方向,以成骨细胞前体细胞-成骨微环境-信号通路及细胞因子作为研究要素,探索各部分要素在不同时空条件下的特征,比较不同种类、不同个体细胞成骨内稳态异同,从整体视角观察异位骨化分子信号网络调控机制,有利于未来临床防治异位骨化新方法的探究。④以中医药及靶向治疗为代表的治疗方法是近年的研究热点,如何将中医药与体内成骨稳态联系,并与靶向治BACKGROUND:Heterotopic ossification is a dynamic growth process.Diverse heterotopic ossification subtypes have diverse etiologies or induction factors,but they exhibit a similar clinical process in the intermediate and later phases of the disease.Acquired heterotopic ossification produced by trauma and other circumstances has a high incidence.OBJECTIVE:To summarize the molecular biological mechanisms linked to the occurrence and progression of acquired heterotopic ossification in recent years.METHODS:The keywords“molecular biology,heterotopic ossification,mechanisms”were searched in CNKI,Wanfang,PubMed,Embase,Web of Science,and Google Scholar databases for articles published from January 2016 to August 2022.Supplementary searches were conducted based on the obtained articles.After the collected literature was screened,131 articles were finally included and summarized.RESULTS AND CONCLUSION:(1)The occurrence and development of acquired heterotopic ossification is a dynamic process with certain concealment,making diagnosis and treatment of the disease difficult.(2)By reviewing relevant literature,it was found that acquired heterotopic ossification involves signaling pathways such as bone morphogenetic protein,transforming growth factor-β,Hedgehog,Wnt,and mTOR,as well as core factors such as Runx-2,vascular endothelial growth factor,hypoxia-inducing factor,fibroblast growth factor,and Sox9.The core mechanism may be the interaction between different signaling pathways,affecting the body’s osteoblast precursor cells,osteoblast microenvironment,and related cytokines,thereby affecting the body’s bone metabolism and leading to the occurrence of acquired heterotopic ossification.(3)In the future,it is possible to take the heterotopic ossification-related single-cell osteogenic homeostasis as the research direction,take the osteoblast precursor cells-osteogenic microenvironment-signaling pathways and cytokines as the research elements,explore the characteristics of each element under different temporal and spatial

关 键 词：异位骨化 分子生物学机制 骨形态发生蛋白 转化生长因子β HEDGEHOG WNT/Β-CATENIN Runt相关转录因子2 血管内皮生长因子 低氧诱导因子 成纤维细胞生长因子 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学] R364