白细胞介素3在骨代谢中的作用及机制

Role and mechanism of interleukin-3 in bone metabolism

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。

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.