中国组织工程研究

中国组织工程研究 ›› 2023, Vol. 27 ›› Issue (19): 3040-3051.doi: 10.12307/2023.635

• 干细胞综述 stem cell review • 上一篇    

外泌体miRNA参与脊柱关节退行性疾病修复的机制

赵  延1，夏秋秋1，向少杰1，毛启名1，孔维军2，杜  迁2，廖文波2，辛志军1   

  1. 1遵义医科大学附属医院骨科，贵州省遵义市   563000；2遵义医科大学第二附属医院骨科，贵州省遵义市   563000
  • 收稿日期:2022-07-22 接受日期:2022-08-27 出版日期:2023-07-08 发布日期:2022-11-28
  • 通讯作者: 辛志军，博士，科室副主任，主任医师，教授，遵义医科大学附属医院骨科，贵州省遵义市 563000
  • 作者简介:赵延，男，1993年生，甘肃省陇南市人，汉族，遵义医科大学在读硕士，主要从事椎间盘退行性病变的基础研究。
  • 基金资助:
    贵州省科学技术基金项目(黔科合平台人才[2017]5733-076)，项目负责人：辛志军；遵义医科大学博士启动资金项目[院字(2022)9号]，项目负责人：辛志军；贵州省科技厅项目(黔科合平台人才-CXTD[2021]009)，项目负责人：廖文波

Exosomal miRNA in the repair mechanism of degenerative diseases of the spine and joints

Zhao Yan1, Xia Qiuqiu1, Xiang Shaojie1, Mao Qiming1, Kong Weijun2, Du Qian2, Liao Wenbo2, Xin Zhijun1   

  1. 1Department of Orthopedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China; 2Department of Orthopedic Surgery, The Second Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
  • Received:2022-07-22 Accepted:2022-08-27 Online:2023-07-08 Published:2022-11-28
  • Contact: Xin Zhijun, MD, Chief physician, Professor, Department of Orthopedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
  • About author:Zhao Yan, Master candidate, Department of Orthopedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
  • Supported by:
    Guizhou Science and Technology Fund Project, No. [2017]5733-076 (to XZJ); Doctoral Start-up Fund Project of Zunyi Medical University, No. (2022)9 (to XZJ); Project of the Department of Science and Technology of Guizhou Province, No. CXTD[2021]009 (to LWB)

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摘要：


文题释义：

外泌体：是细胞通过出芽方式分泌的具有双层磷脂膜结构的纳米级(直径40-120 nm)囊性小泡，包含母细胞的细胞因子、蛋白、脂类、mRNA、miRNA(microRNA)及非编码RNA等信息分子，其渗透性与稳定性良好，能够远程或局部与靶细胞融合。
miRNA：是一类由19-25个核苷酸组成的非编码单链RNA，通过降解靶基因mRNA或阻遏mRNA的蛋白翻译对靶基因在细胞中差异性表达，进而调控下游通路的激活以获得效能。

背景：脊柱关节退行性病变主要包括椎间盘退行性病变和骨关节炎，近年来利用外泌体miRNA通过促进细胞的自噬和增殖、迁移等治疗脊柱关节退行性病变已成为具有前景的新兴治疗手段。
目的：综述外泌体miRNA在椎间盘退行性病变和骨关节炎的疾病发展、诊断及治疗机制的研究进展。
方法：第一作者以“Intervertebral disc degeneration，Osteoarthritis，Exosomes，miRNA，Autophagy，Extracellular matrix，Apoptosis，Cell proliferation，Pyroptosis，Biomarkers，Mechanistic pathways”为检索词检索PubMed数据库，最终纳入133篇英文文献进行归纳总结。
结果与结论：①外泌体miRNA治疗脊柱关节退行性疾病的主要作用机制是通过促进自噬和细胞的迁移和增殖，抑制细胞外基质降解、细胞凋亡、细胞焦亡及炎症反应等多个方面发挥对脊柱关节退行性疾病的治疗作用，并且同一外泌体miRNA能够参与同一疾病的不同生理病理过程；②Wnt/β-catenin途径、mTOR、NLRP3、核转录因子κB及MAPK等信号通路在外泌体治疗脊柱关节退行性病变中发挥重要作用，其中MAKP信号通路是外泌体miRNA治疗改善椎间盘退行性病变和骨关节炎疾病进程中共同存在的信号通路，对于寻找椎间盘退行性病变、骨关节炎疾病及其他脊柱关节退行性疾病的共同靶点具有重要启示意义；③同一miRNA家族可参与不同的退行性病变的修复，对于探索或合成新型外泌体miRNA来治疗其他脊柱关节退行性疾病具有重要的借鉴意义，但未来需进一步明确外泌体miRNA对脊柱关节退行性疾病的安全性和不良反应。
https://orcid.org/0000-0002-4763-6634 (赵延)；https://orcid.org/0000-0003-4714-6691 (辛志军)
中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 椎间盘退行性病变, 骨关节炎, 外泌体, miRNA, 自噬, 细胞外基质, 细胞凋亡, 细胞焦亡, 细胞增殖, 生物标志物

Abstract: BACKGROUND: Degenerative spondylolisthesis mainly consists of intervertebral disc degeneration and osteoarthritis. In recent years, the use of exosomal miRNAs to treat degenerative spinal joint disease by promoting autophagy and cell proliferation and migration has become a promising emerging therapeutic option.  
OBJECTIVE: To review the research progress of exosomal miRNA in the development, diagnosis and treatment mechanism of intervertebral disc degeneration and osteoarthritis.
METHODS: The first author searched the PubMed database using “intervertebral disc degeneration; osteoarthritis; exosomes; miRNA; autophagy; extracellular matrix; apoptosis; cell proliferation; pyroptosis; biomarkers; mechanistic pathways” as the keywords. Finally, 133 English articles were summarized.  
RESULTS AND CONCLUSION: (1) The main physiopathological feature of exosomal miRNA for the treatment of degenerative spinal joint diseases is to treat degenerative spinal joint diseases by promoting autophagy and cell migration and proliferation, inhibiting extracellular matrix degradation, apoptosis, cell pyroptosis and inflammatory effects in several ways. The same exosomal miRNA is able to participate in different physiopathological processes of the same disease. (2) The mechanisms and pathways of action of exosomes in the treatment of degenerative spondylolisthesis occur mainly through the Wnt/β-catenin pathway, mTOR, NLRP3, nuclear factor-κB, MAPK and other signaling pathways; the MAKP signaling pathway is a common signaling pathway in exosomal miRNA therapy to improve the process of intervertebral disc degeneration and osteoarthritis disease, which is significant for finding common targets in intervertebral disc degeneration, osteoarthritis disease and other degenerative diseases of the spine and joints. (3) The same miRNA family can be involved in the repair of different degenerative lesions, which has a significant implication for the exploration or synthesis of new type of exosomal miRNA to treat other degenerative diseases of the spine and joints, but further studies are needed to investigate the safety and adverse effects of exosomal miRNA therapy in spinal and joint degenerative diseases.

Key words: intervertebral disc degeneration, osteoarthritis, exosome, miRNA, autophagy, extracellular matrix, apoptosis, cell pyroptosis, cell proliferation, biomarker

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