外泌体在骨不连治疗中的作用机制及进展

doi:10.3969/j.issn.2095-4344.2801

中国组织工程研究 ›› 2020, Vol. 24 ›› Issue (27): 4349-4355.doi: 10.3969/j.issn.2095-4344.2801

• 骨与关节综述 bone and joint review • 上一篇下一篇

外泌体在骨不连治疗中的作用机制及进展

赖渝1，韩杰2

1广西中医药大学附属瑞康医院，广西壮族自治区南宁市 530011；2广西中医药大学附属瑞康医院关节与运动医学科，广西壮族自治区南宁市 530011

收稿日期:2019-12-30 修回日期:2020-01-07 接受日期:2020-02-26 出版日期:2020-09-28 发布日期:2020-09-09
通讯作者: 韩杰，副主任医师，硕士生导师，广西中医药大学附属瑞康医院关节与运动医学科，广西壮族自治区南宁市 530011
作者简介:赖渝，男，1996年生，江西省赣州市人，广西中医药大学在读硕士，主要从事骨与关节疾病及运动损伤研究。
基金资助:
国家自然科学基金资助项目(81760796，81960803)；广西高校青年教师基础能力提升项目(2019KY0352)；广西中医药大学2019年校级科研课题(2019QN027)；广西中医药大学一流学科课题(2019XK029)

Mechanism and progress of exosomes in the treatment of nonunion

Lai Yu1, Han Jie2

1Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China; 2Department of Joint and Sports Medicine, Ruikang Hospital, Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China

Received:2019-12-30 Revised:2020-01-07 Accepted:2020-02-26 Online:2020-09-28 Published:2020-09-09
Contact: Han Jie, Associate chief physician, Master’s supervisor, Department of Joint and Sports Medicine, Ruikang Hospital, Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
About author:Lai Yu, Master candidate, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
Supported by:
the National Natural Science Foundation of China, No. 81760796, 81960803; the Basic Ability Improvement Project of Young Teachers from Guangxi Universities, No. 2019KY0352; the School-Level Scientific Research Project of Guangxi University of Chinese medicine in 2019, No. 2019QN027; the First-Class Discipline Project of Guangxi University of Chinese medicine, No. 2019XK029

摘要/Abstract

摘要：

文题释义：

外泌体：是细胞外囊泡小体，由不同类型的细胞释放，根据其自身各种特性，可运用于损伤组织间药物的传递，作为生物标志物，介导细胞间信息交流等巨大作用。

哺乳动物雷帕霉素靶蛋白信号通路：哺乳动物雷帕霉素靶蛋白(mTOR)是一种蛋白激酶，其催化亚单位是2种生化上截然不同的复合物mTORC1和mTORC2，对骨形成的调节非常重要。

背景：骨不连是骨折术后常见的并发症，给患者带来了极大的困扰。随着外泌体技术的不断研发，外泌体在骨不连的治疗中逐渐显露优势，成为医疗工作新的研究方向。

目的：从国内外研究中归纳总结，探讨外泌体在骨不连治疗中的作用。

方法：中文以“外泌体，骨不连，骨重塑，骨再生，血管损伤，成骨细胞，破骨细胞”检索万方、中国知网、维普文献数据2003至2019年的相关文献，英文以“exosomes，nonunion，bone remodelling”，检索PubMed数据库2003至2019年的相关文献，根据纳入及排除标准摘选50篇文章。

结果与结论：①近年来，外泌体作用于骨不连的研究得到越来越多的重视，外泌体中的miRNA及蛋白质可以通过影响骨细胞的分化作用于骨不连；②随着进一步的研究发现，外泌体可通过调节骨重塑，促进血管修复，改善系统性疾病等方面治疗骨不连；③但是目前对于外泌体的研究仍处于实验阶段，如何将其更好地应用于临床治疗还需进一步的探究。

ORCID: 0000-0003-0172-7642(赖渝)

中国组织工程研究杂志出版内容重点：人工关节；骨植入物；脊柱；骨折；内固定；数字化骨科；组织工程

关键词: 外泌体, 骨不连, miRNA, 骨重塑, 血管损伤

Abstract:

BACKGROUND: Bone nonunion is a common complication after fracture, which brings great distress to patients. With the continuous development of exosomal technology, exosomes gradually show their advantages in the treatment of nonunion, which has become a new research direction in medical work.

OBJECTIVE: To summarize the researches in and outside China and explore the role of exosomes in the treatment of nonunion.

METHODS: The authors retrieved related Chinese articles published from 2003 to 2019 in Wanfang database, CNKI and VIP database with the key words of “exosomes, nonunion, bone remodeling, bone regeneration, vascular injury, osteoblasts, osteoclasts” and related English articles published from 2003 to 2019 in PubMed with the key words of “exosomes, nonunion, bone remodeling”. Totally 50 articles were selected based on inclusion and exclusion criteria.

RESULTS AND CONCLUSION: (1) In recent years, more and more attention has been paid to the study of exosomes on bone nonunion. MiRNAs and proteins in exosomes can affect bone nonunion by affecting the differentiation of osteocytes. (2) Studies have found that exosomes can treat bone nonunion by regulating bone remodeling, promoting vascular repair, and improving systemic diseases. (3) However, the current research on exosomes is still in the experimental stage. The specific method of how to better apply it to clinical treatment needs further exploration.

Key words: exosomes, bone nonunion, miRNA, bone remodeling, vascular injury

中图分类号:

赖渝, 韩杰. 外泌体在骨不连治疗中的作用机制及进展[J]. 中国组织工程研究, 2020, 24(27): 4349-4355.

Lai Yu, Han Jie. Mechanism and progress of exosomes in the treatment of nonunion[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(27): 4349-4355.

图/表（结果） 3

1.3 质量评估计算机检索共得到214篇相关文献，根据标题及摘要进行初步筛选，排除重复性研究和年代久远的文献。最终根据标准共纳入50篇文章。仔细阅读文章内容，总结有效信息并严谨撰写文章。文献检索流程图见图1。

2.2.1 外泌体的来源外泌体是细胞外囊泡小体，直径为40-100 nm^[4]，由不同类型的细胞释放，如巨噬细胞、肿瘤细胞、神经细胞、T细胞等，同时最近研究表明，骨相关细胞，包括破骨细胞、成骨细胞、骨髓间充质干细胞等细胞也分泌外体^[5]。除此之外，在体液如尿液、血液、羊水、恶性腹水、支气管肺泡灌洗液、滑液和母乳中也发现了外泌体^[6]。外泌体的形成和传递是由供体细胞的质膜内化产生的内吞小体(Endosomes)开始，然后蛋白质和RNA(包括lncRNA、circRNA、mRNA和miRNA)通过转运所需的内体分选复合物依赖性或内体分选复合物非依赖性机制选择性地被装入多泡体内。随后，多泡体或者融合到溶酶体上进行降解，或者通过与质膜融合释放到细胞外空间以产生外泌体。随后，外泌体通过特异性识别进入受体细胞，将转运物质释放，其具体传递过程见图2^[7-8]。外泌体的成分中含有一些根据供体细胞类型而改变的生物活性分子，同时外泌体富含一些来自于分泌细胞的成分，如mRNAs、IncRNAs、circRNAs、脂质、蛋白质、DNA等，它们在信息传递过程中起到了重要作用。

2.4 外泌体在骨重塑的调节作用通过对骨不连的发生机制可以得出，骨折端不愈合的诱发因素之一就是骨折端的骨代谢遭到破坏。所以，解决骨重塑在骨折恢复期的问题成为治疗骨不连的一个研究方向。而骨源性外泌体通过转移破骨细胞和成骨细胞分化和交流所需的分子，参与调节骨重塑，作用示意图见图3^[32]。

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外泌体在骨不连治疗中的作用机制及进展

Mechanism and progress of exosomes in the treatment of nonunion

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