巨噬细胞的骨免疫学效应

Osteoimmunological effects of macrophages

背景:巨噬细胞以其显著的骨免疫学效应得到学者们的广泛关注,其功能和应用已成为研究热点。目前研究主要涉及巨噬细胞的起源、极化、骨免疫学效应及其在骨修复中的应用。目的:综述巨噬细胞的骨免疫学效应及其在骨修复中应用的研究进展,证实巨噬细胞在骨组织工程中具有卓越的研究价值和应用前景。方法:利用PubMed、Web of Science和CNKI数据库检索2010-2022年发表的相关文献,检索词为“巨噬细胞极化、骨、成骨、骨免疫学、生物材料、组织工程”“macrophage polarization,bone,osteogenesis,osteoimmunology,biomaterials,tissue engineering”,并纳入少量年份久远的经典文献。通过阅读标题和摘要进行初筛,排除与文章主题不相关的文献,最终纳入120篇文献进行综述分析。结果与结论:①巨噬细胞包括单核细胞来源的炎性巨噬细胞和组织驻留巨噬细胞,其中不同组织的驻留巨噬细胞具有不同的发育起源组合,绝大多数组织驻留巨噬细胞起源于胚胎时期的卵黄囊;②巨噬细胞具有高度可塑性,在不同刺激下极化为M1/M2表型,分别释放促炎/抗炎因子,且巨噬细胞极化受到AMPK-mTOR、Notch、MAPK、STAT、NF-кB、Akt等多条信号通路的调节;③巨噬细胞的骨免疫学效应涉及巨噬细胞与骨骼细胞之间的串扰,通过对生物材料刚度、粗糙度、孔径、亲水性等理化性质的修饰或结合药物、细胞因子、金属离子、microRNA等单一或多种生物活性物质,实现巨噬细胞的骨免疫学效应在骨修复中的有效利用。

BACKGROUND:Macrophages have received extensive attention from scholars for their remarkable osteoimmunological effects,and their functions and applications have become a research hot spot.The current research mainly involves the origin,polarization and osteoimmunological effects of macrophages and their applications in bone repair.OBJECTIVE:To confirm the outstanding research value and application prospects of macrophages in bone tissue engineering through reviewing research advances in osteoimmunological effects of macrophages and their applications in bone repair.METHODS:PubMed,Web of Science and CNKI databases were used to search the related articles published from 2010 to 2022.The search terms were“macrophage polarization,bone,osteogenesis,osteoimmunology,biomaterials,tissue engineering”.The searches to English and Chinese language publications were limited.A small number of old classic literature was also included.An initial screening was performed by reading the titles and abstracts to exclude literature that was not relevant to the topic of the article,and 120 papers were finally included for the analysis of the results.RESULTS AND CONCLUSION:(1)Macrophages include monocyte-derived inflammatory macrophages and tissue-resident macrophages,of which different tissue-resident macrophages have different combinations of developmental origins;most tissue-resident macrophages originate from the yolk sac during the embryonic period.(2)Macrophages,highly pastic cells,undergo M1 or M2 macrophage polarization and release pro-or anti-inflammatory factors in response to different stimuli.Alternatively,macrophage polarization is regulated by multiple signaling pathways,including the AMPK-mTOR,Notch,MAPK,STAT,NF-кB,and Akt signaling pathways.(3)The osteoimmunological effects of macrophages involve the crosstalk between macrophages and skeletal cells.The effective application of osteoimmunological effects of macrophages in bone repair can be realized by modifying the physicochemical properties of biomaterials such as stiffness,roughness,pore size,and hydrophilicity or by combining single or multiple biologically active substances such as drugs,cytokines,metal ions,and microRNAs.