中国组织工程研究

中国组织工程研究 ›› 2023, Vol. 27 ›› Issue (2): 314-321.doi: 10.12307/2022.1006

• 组织构建综述 tissue construction review • 上一篇    下一篇

M2巨噬细胞参与骨再生相关信号通路的作用与机制

张  洁1，田  艾1，2   

  1. 1贵州医科大学口腔医学院，贵州省贵阳市  550001；2贵州医科大学附属口腔医院修复种植科，贵州省贵阳市  550001
  • 收稿日期:2022-02-10 接受日期:2022-03-03 出版日期:2023-01-18 发布日期:2022-06-20
  • 通讯作者: 田艾，博士，副教授，副主任医师，贵州医科大学附属口腔医院修复种植科，贵州省贵阳市 550001
  • 作者简介:张洁，女，1996年生，贵州省贵阳市人，汉族，贵州医科大学在读硕士。
  • 基金资助:
    国家自然科学基金资助项目(81760192)，项目负责人：田艾；贵阳市科技局联合基金([2018]1-82)，项目负责人：田艾；贵州医科大学博士启动资金(YJ2016-16)，项目负责人：田艾

Advances in the signaling pathway of M2 macrophages involved in bone regeneration

Zhang Jie1, Tian Ai1, 2   

  1. 1School of Stomatology, Guizhou Medical University, Guiyang 550001, Guizhou Province, China; 2Department of Restoration and Implant, Affiliated Stomatological Hospital of Guizhou Medical University, Guiyang 550001, Guizhou Province, China
  • Received:2022-02-10 Accepted:2022-03-03 Online:2023-01-18 Published:2022-06-20
  • Contact: Tian Ai, MD, Associate professor, Associate chief physician, School of Stomatology, Guizhou Medical University, Guiyang 550001, Guizhou Province, China; Department of Restoration and Implant, Affiliated Stomatological Hospital of Guizhou Medical University, Guiyang 550001, Guizhou Province, China
  • About author:Zhang Jie, Master candidate, School of Stomatology, Guizhou Medical University, Guiyang 550001, Guizhou Province, China
  • Supported by:
    the National Natural Science Foundation of China, No. 81760192 (to TA); Joint Fund of Guiyang Science and Technology Bureau, No. [2018]1-82 (to TA); Guizhou Medical University Doctoral Start-up Fund, No. YJ2016-16 (to TA)

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摘要：

文题释义：
巨噬细胞极化：巨噬细胞会受到微环境中多种因子的调节与诱导，从而可以产生不同的功能状态，这种功能可塑性称为巨噬细胞极化。炎性巨噬细胞被称为经典激活的或M1巨噬细胞，而活跃于组织再生的巨噬细胞为交替激活的或M2巨噬细胞。
骨再生：在骨重建过程中，通过基本多细胞单位的重塑作用对破骨细胞和成骨细胞进行协调，以实现破骨细胞定点清除受损/低质量骨，并随后由成骨细胞替换成新骨，整合到现有结构单元中。

背景：研究M2巨噬细胞诱导骨再生的分子机制，整理分析多条信号通路的综合性基因调控网络，对于靶向调控骨替代材料介导的免疫反应从而促进牙槽骨缺损修复具有重要意义。
目的：综述国内外相关文献，总结M2巨噬细胞在骨再生中的相关信号通路的研究进展，以期为临床牙槽骨缺损患者的再生治疗找到准确和主动的免疫调节策略。 
方法：检索CNKI、Web of Science和PubMed数据库收录的相关文献。英文检索词为“macrophages，polarization ，bone regeneration，osteogenesis，signaling pathway”；中文检索词为“巨噬细胞极化，信号通路，骨再生，成骨”。按入选标准筛选后纳入55篇文章进行综述。
结果与结论：①巨噬细胞在骨愈合中的作用是复杂的，通过微调和精确的策略将M0/M1巨噬细胞切换到M2表型，导致形成适当的M2优势更加有利于骨再生。一旦M2巨噬细胞表型发生改变，它们的细胞表面标志物、分泌的细胞因子和趋化因子以及转录和表观遗传途径(信号通路)均产生相应变化。②文章总结分析了近7年来各类信号通路参与M2巨噬细胞极化从而诱导骨缺损修复或成骨分化的相关分子机制。各信号通路在参与或调控骨代谢过程中的炎症反应、成骨和软骨分化等发挥重要的作用。大量的体内外研究表明，靶向调控信号通路可能是针对巨噬细胞极化促进骨再生的有效途径。③进一步的临床研究还需要阐明调节信号通路以有利于降低M1/M2巨噬细胞比率可能是促进牙槽骨缺损修复的有效途径。一旦这种机制被明确阐明，针对巨噬细胞极化状态的药理学和新型生物材料可能被用作促进骨再生的策略。

https://orcid.org/0000-0003-4456-1144 (张洁) 

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

关键词: 巨噬细胞极化, 信号通路, 骨再生, 成骨, 综述

Abstract: BACKGROUND: Studying the molecular mechanisms of M2 macrophage-induced bone regeneration and collating and analyzing the comprehensive gene regulatory network of multiple signaling pathways are important for targeting and regulating the immune response mediated by bone replacement materials to promote alveolar bone defect repair.
OBJECTIVE: To review relevant literature and summarize the research progress in relevant signaling pathways of M2 macrophages in bone regeneration, in order to find accurate and proactive immunomodulatory strategies for the regenerative treatment of alveolar bone defects in clinical settings.
METHODS: Relevant literature in CNKI, Web of Science and PubMed were searched. Search terms were “macrophages, polarization, bone regeneration, osteogenesis, signaling pathway” in Chinese and English. According to the inclusion criteria, 55 articles were included for review.
RESULTS AND CONCLUSION: The role of macrophages in bone healing is complex, and switching M0/M1 macrophages to the M2 phenotype through a fine-tuned and precise strategy leads to the formation of an appropriate M2 dominance, which is more conducive to bone regeneration. Once the M2 macrophage phenotype is altered, their cell surface markers, secreted cytokines and chemokines, as well as transcriptional and epigenetic pathways (signaling pathways) are changed accordingly. The article summarizes the molecular mechanisms involved in the polarization of M2 macrophages and thus inducing bone defect repair or osteogenic differentiation by various signaling pathways over the past 7 years. Each signaling pathway plays an important role in participating in or regulating the inflammatory response, osteogenesis and chondrogenic differentiation during bone metabolism. Numerous in vivo and ex vivo studies have shown that targeting and modulating signaling pathways may be an effective way to promote bone regeneration by targeting macrophage polarization. Further clinical studies are needed to elucidate whether modulating signaling pathways in favor of reducing the M1/M2 macrophage ratio may be an effective way to promote alveolar bone defect repair. Once this mechanism is clearly elucidated, pharmacology and novel biomaterials targeting the macrophage polarization state may be used as a strategy to promote bone regeneration.

Key words: macrophage polarization, signaling pathway, bone regeneration, osteogenesis, review

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