白细胞介素33介导的骨免疫  

Interleukin-33-mediated bone immunity

作　　者：沈梦然 任岩松 周宇 岳德波[2] 马金辉[2] 王佰亮[2] Shen Mengran;Ren Yansong;Zhou Yu;Yue Debo;Ma Jinhui;Wang Bailiang(Peking University China-Japan Friendship School of Clinical Medicine,Beijing 100029,China;Department of Orthopedic Surgery,China-Japan Friendship Hospital,Beijing 100029,China)

机构地区：[1]北京大学中日友好临床医学院,北京市100029 [2]中日友好医院骨科,北京市100029

出　　处：《中国组织工程研究》2023年第29期4723-4728,共6页Chinese Journal of Tissue Engineering Research

基　　金：中央高校基本科研业务费—青年教师项目(3332021088),项目负责人:马金辉;中央高水平医院临床科研业务费,中日友好医院“菁英计划”人才培育工程项目(ZRJY2021-TD01),项目负责人:王佰亮。

摘　　要：背景:骨免疫学是近年来骨代谢疾病机制研究的热点。白细胞介素33是骨免疫学中的一个重要的新型细胞因子,在类风湿关节炎、骨质疏松等多种骨代谢疾病进展中发挥重要作用,其传导通路可能成为临床治疗的潜在靶点。目的:综述白细胞介素33在骨代谢过程中的骨免疫调节作用及其研究进展。方法:检索PubMed、Web of Science、中国知网及万方数据库从建库至2022年6月收录的白细胞介素33和骨代谢及骨免疫学研究相关文献,最终纳入67篇文献进行总结。结果与结论:①白细胞介素33介导骨免疫对骨代谢具有调节作用。②白细胞介素33对骨代谢的调节可通过降低硬化蛋白的表达,进而激活成骨细胞Wnt/β-catenin通路,该途径通过多种机制增加骨量,包括干细胞更新、刺激成骨细胞前复制、诱导成骨细胞生成、抑制成骨细胞和骨细胞凋亡。白细胞介素33可通过刺激Bcl6、MafB、Irf-8等抗破骨细胞基因的表达,下调破骨细胞活性T细胞核因子c1的表达,进而抑制破骨细胞的形成,并且可诱导凋亡分子的表达,促进破骨细胞凋亡。③白细胞介素33可下调2型天然淋巴细胞RANKL的表达,促进白细胞介素13、白细胞介素4和粒细胞-巨噬细胞集落刺激因子的产生来抑制破骨细胞的分化。白细胞介素33可诱导调节性T细胞向炎症部位募集,通过抑制Th1、CD8+T细胞和M1巨噬细胞,以支持成骨前体细胞的分化,抑制破骨细胞共刺激分子的表达,导致破骨细胞的分化和功能受到抑制。白细胞介素33可激活幼稚T细胞向Th2型表型分化,产生Th2型细胞因子,可诱导破骨细胞在局部的募集,造成局部骨吸收增加,软骨退化。④白细胞介素33可诱导内皮细胞增殖、迁移和形态分化,促进血管形成,对缺血性疾病有一定的保护作用。⑤白细胞介素33对骨代谢的调节具有双向性,造成骨代谢紊乱的病因多样,并且体内不同部位微BACKGROUND:Osteoimmunology is a hot spot in the research on the mechanism of bone metabolic diseases in recent years.Interleukin-33 is an important new cytokine in bone immunology.It plays an important role in the progression of various bone metabolic diseases such as rheumatoid arthritis and osteoporosis.Its conduction pathway may become a potential target for clinical treatment.OBJECTIVE:To review the research progress of interleukin-33 in osteoimmunology effect during bone metabolism.METHODS:The articles related to interleukin-33,bone metabolism,and osteoimmunology were searched in PubMed,Web of Science,WanFang,and CNKI databases from the establishment of the database to June 2022,and finally 67 articles were included and summarized.RESULTS AND CONCLUSION:(1)Interleukin-33 mediated bone immunity has a regulatory effect on bone metabolism.(2)Regulation of bone metabolism by interleukin-33 can activate the osteoblast Wnt/β-catenin pathway by reducing the expression of sclerostin.This pathway increases bone mass through a variety of mechanisms,including stem cell renewal,stimulation of pre-osteoblast replication,induction of osteoblastogenesis,inhibition of osteoblast and osteocyte apoptosis.Interleukin-33 can inhibit the expression of nuclear factor of activated T cells c1 and osteoclast formation by stimulating the expression of antiosteoclast genes such as Irf-8,MafB,and Bcl6.Moreover,the expression levels of apoptosis molecules can be induced,resulting in osteoclast apoptosis.(3)Interleukin-33 can inhibit the expression of RANKL in type 2 innate lymphocytes and induce the production of interleukin-13,interleukin-4,and granulocytemacrophage colony stimulating factor,thereby inhibiting the differentiation of osteoclasts.Interleukin-33 can induce the recruitment of regulatory T cells to inflammatory sites and inhibit Th1 cells,CD8+T cells,and M1 macrophages to support the differentiation of osteogenic precursor cells and inhibit the expression of osteoclast costimulatory molecules,thereby suppressing osteoclast

关 键 词：白细胞介素33 骨免疫 成骨细胞 破骨细胞 淋巴细胞 内皮细胞 

分 类 号：R459.9[医药卫生—治疗学] R392[医药卫生—临床医学] R68