中国组织工程研究 ›› 2022, Vol. 26 ›› Issue (8): 1260-1265.doi: 10.12307/2022.233

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

白细胞介素3在骨代谢中的作用及机制

王  景1,熊  山1,曹  金1,冯林伟2,王  信1   

  1. 1遵义医科大学附属医院骨科,贵州省遵义市   563003;2重庆市南川区中医医院,重庆市   408400
  • 收稿日期:2021-06-17 修回日期:2021-06-21 接受日期:2021-07-09 出版日期:2022-03-18 发布日期:2021-11-02
  • 通讯作者: 王信,博士,主任医师,博士生导师,遵义医科大学附属医院骨科,贵州省遵义市 563003 冯林伟,主治医师,重庆市南川区中医医院骨伤科,重庆市 408400
  • 作者简介:王景,男,1995年生,安徽省安庆市人,汉族,遵义医科大学在读硕士,主要从事骨缺损早期愈合的基础研究。 熊山,男,1997年生,重庆市人,汉族,遵义医科大学在读硕士,主要从事骨缺损早期愈合的基础研究。
  • 基金资助:
    国家自然科学基金(31960209,31760266),项目负责人:王信;贵州省科技厅基础研究计划(黔科合基础[2020]1Y093),项目负责人:王信

Role and mechanism of interleukin-3 in bone metabolism

Wang Jing1, Xiong Shan1, Cao Jin1, Feng Linwei2, Wang Xin1   

  1. 1Department of Orthopedics, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China; 2Nanchuan District Hospital of Traditional Chinese Medicine, Chongqing 408400, China
  • Received:2021-06-17 Revised:2021-06-21 Accepted:2021-07-09 Online:2022-03-18 Published:2021-11-02
  • Contact: Wang Xin, MD, Chief physician, Doctoral supervisor, Department of Orthopedics, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China Feng Linwei, Attending physician, Nanchuan District Hospital of Traditional Chinese Medicine, Chongqing 408400, China
  • About author:Wang Jing, Master candidate, Department of Orthopedics, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China Xiong Shan, Master candidate, Department of Orthopedics, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
  • Supported by:
    the National Natural Science Foundation of China, No. 31960209 and 31760266 (both to WX); Basic Research Program of Guizhou Science and Technology Department, No. [2020]1Y093 (to WX)

摘要:

文题释义:
白细胞介素3:是白细胞介素家族的重要的成员之一,是一种具有多谱系潜力的广谱靶细胞因子,不仅在免疫反应中发挥作用,而且其对骨代谢的过程也会产生一定的影响。
成骨:小的骨发生缺损后,机体自动实现的骨再生愈合的过程。其中独特的分子机制会产生对成骨作用的精密调节作用,更好地促进骨再生过程。
骨稳态:是由成骨性成骨细胞和吸收骨的破骨细胞之间相互串扰严格控制的骨重塑的一个动态过程,其中破骨细胞吸收旧的或受损的骨骼,并用成骨细胞形成的新生骨骼代替。作为骨形成细胞,成骨细胞通过一系列细胞因子的连续作用从间充质前体骨髓系到终末分化为成熟的成骨细胞。
背景:骨缺损与骨愈合一直是临床上面临的重大问题。近年来,临床开始使用靶向细胞因子如白细胞介素3来治疗特定骨疾病,如类风湿关节炎和多发性骨髓瘤等。
目的:总结白细胞介素3与骨代谢之间的关系,了解白细胞介素3在成骨中的作用机制,为新的成骨方案提供理论参考。
方法:由第一作者检索PubMed数据库(1990年1月至2021年3月)及中国知网数据库(1979年1月至2021年3月),检索与白细胞介素3在成骨相关代谢中的作用机制相关的文献。英文检索词为“Interleukin 3,bone metabolism,osteoblast,osteoclast,bone formation,Mesenchymal stem cells,Vascularization”,中文检索词为“白细胞介素3,骨形成,成骨细胞,破骨细胞,骨代谢”,初检得到中英文文章896篇,按纳入排除标准共纳入56篇文章进行综述分析。
结果与结论:①与其他细胞因子不同,白细胞介素3具有多谱系靶向潜力,在造血系统中起重要作用。②研究发现白细胞介素3可以直接作用于间充质干细胞,促进其成骨分化。此外,也有研究发现白细胞介素3可以刺激骨形态发生蛋白2的合成,正向调节间充质干细胞的成骨分化。虽然白细胞介素3通过对骨形态发生蛋白2的抑制作用产生对骨髓基质成骨细胞的影响,但未发现白细胞介素3对Runx2和β-catenin途径产生的效应。③破骨细胞吸收骨会造成骨流失,早期研究发现白细胞介素3产生促进破骨细胞的作用,而近期研究表明白细胞介素3在mRNA和蛋白水平上显著抑制c-Fms,并下调PU.1和c-Fos表达,从而产生对破骨细胞的抑制作用。④因此,文章深入综述白细胞介素3在成骨细胞和破骨细胞中的具体作用机制,以期为接下来的研究提供借鉴或参考。

https://orcid.org/0000-0001-6745-5411 (王景) ;https://orcid.org/0000-0001-5015-3396 (王信)

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: 白细胞介素3, 成骨, 骨形成, 成骨细胞, 破骨细胞, 间充质干细胞, 血管化, 综述

Abstract: BACKGROUND: Bone defect and bone healing have always been two major clinical problems. In recent years, targeted cytokines such as Interleukin-3 have been used to treat certain bone diseases, such as rheumatoid arthritis and multiple myeloma.
OBJECTIVE: To summarize the relationship between interleukin-3 and bone metabolism, and to understand the mechanism of interleukin-3 in osteogenesis, so as to provide theoretical reference for new osteogenesis programs.
METHODS: PubMed and CNKI were retrieved by the first author for relevant articles published January 1990 to March 2021 and from January 1979 to March 2021, respectively. The search terms used were “interleukin-3, bone metabolism, osteoblast, osteoclast, bone formation, mesenchymal stem cells, vascularization” in English and Chinese, respectively. A total of 896 articles detailing the mechanism of interleukin-3 and osteogenesis related metabolism were initially searched, and finally 56 eligible articles were included for further review and analysis. 
RESULTS AND CONCLUSION: Different from other cytokines, interleukin-3 has multi-lineage targeting potential and plays an important role in hematopoietic system. Studies have shown that interleukin-3 can directly interact with mesenchymal stem cells and promote their osteogenic differentiation. In addition, interleukin-3 has been shown to positively regulate the osteogenic differentiation of mesenchymal stem cells by stimulating the synthesis of bone morphogenetic protein-2. Although interleukin-3 has an effect on bone marrow stromal osteoblasts through inhibition of bone morphogenetic protein-2, no effects of interleukin-3 on the Runx2 and β-catenin pathways have been found. Bone absorption by osteoclasts can lead to bone loss. Early studies found that interleukin-3 could promote osteoclasts, while recent studies have shown that interleukin-3 could significantly inhibit c-Fms at mRNA and protein levels, and down-regulate the expressions of PU.1 and c-Fos, thus producing an inhibitory effect on osteoclasts. Therefore, the specific mechanism of interleukin-3 in osteoblasts and osteoclasts is thoroughly reviewed in this paper, with a view to providing references for future studies.

Key words: interleukin-3, osteogenesis, bone formation, osteoblasts, osteoclasts, mesenchymal stem cells, vascularization, review

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