[1]沈作佳 毛建华 徐广 冉强 万锐杰△.白细胞介素-7对巨噬细胞分化形成破骨细胞的影响[J].中国中医骨伤科杂志,2019,27(07):6-9，14.
　SHEN Zuojia MAO Jianhua XU Guang RAN Qiang WAN Ruijie.Effect of Interleukin-7 on the Differentiation of Macrophages into Osteoclasts[J].Chinese Journal of Traditional Medical Traumatology & Orthopedics,2019,27(07):6-9，14.
点击复制

白细胞介素-7对巨噬细胞分化形成破骨细胞的影响()
分享到：

《中国中医骨伤科杂志》[ISSN:1005-0205/CN:42-1340/R]

卷:
第27卷
期数:
2019年07期
页码:
6-9，14
栏目:
实验研究
出版日期:
2019-06-30

文章信息/Info

Title:
Effect of Interleukin-7 on the Differentiation of Macrophages into Osteoclasts
文章编号:
1005-0205(2019)07-0006-04
作者:
沈作佳1 毛建华1 徐广1 冉强2 万锐杰2△
1浙江江山市人民医院骨三科(浙江 江山,324100) 2重庆市中医院骨科
Author(s):
SHEN Zuojia1 MAO Jianhua1 XU Guang1 RAN Qiang2 WAN Ruijie2△
1Department of Orthopedics,Jiangshan People's Hospital,Jiangshan 324100,Zhejiang China; 2Department of Orthopedics,Chongqing Hospital of Traditional Chinese Medicine,Chongqing 400021,China.
关键词:
白细胞介素-7;  破骨细胞;  巨噬细胞;  信号通路
Keywords:
interleukin-7;  osteoclasts;  macrophages;  signaling pathway
分类号:
R-33
文献标志码:
A
摘要:
目的:白细胞介素-7(IL-7)在类风湿关节炎骨破坏过程中具有重要作用,然而IL-7的具体作用方式 不明确,因此本研究分析了IL-7对破骨细胞分化形成的作用及相关分子机制。方法:用M-CSF,M-CSF+RANKL 及IL-7分别诱导RAW264.7巨噬细胞分化形成破骨细胞,通过抗酒石酸酸性磷酸酶(TRAP)染色评价IL-7对破 骨细胞分化形成的影响。然后使用JAK信号通路抑制剂(AG490),AKT信号通路抑制剂(LY294002)和JNK信号 通路抑制剂(SP600125),采用RT-PCR和ELISA分别检测IL-7对破骨细胞骨溶性相关活性基因和蛋白分泌的影 响。最后使用蛋白印迹检测探讨IL-7促进破骨细胞分化形成的相关分子机制。结果:IL-7在核因子κB配体 (RANKL)不存在的情况下能够显著增加破骨细胞的数量。IL-7能够显著诱导破骨细胞溶骨相关活性成分包 括基质金属蛋白酶-9(MMP9)、组织蛋白酶(CathK)、抗酒石酸酸性磷酸酶(TRAP)、降钙素受体(CTR)的基因 表达和蛋白分泌,JAK(AG490)和JNK(SP600125)信号通路抑制剂能显著抑制IL-7诱导的上述基因表达和蛋白 分泌。IL-7显著诱导JAK,AKT及JNK信号通路信号蛋白的活化。结论:IL-7能不依赖于RANKL诱导破骨细胞的 分化形成,其作用可能是通过活化JAK和JNK信号通路实现的。
Abstract:
Interleukin-7(IL-7)plays an important role in the process of bone destruction in rheumatoid arthritis.However,the specific mode of action of IL-7 is not clear.Therefore,this study analyzed the effect of IL-7 on osteoclastogenesis and its related molecular mechanism.Methods:M-CSF,M-CSF+RANKL and IL-7 were used to induce RAW264.7 cells to differentiate into osteoclasts,respectively.The effect of IL-7 on osteoclastogenesis was evaluated by tartrate-resistant acid phosphatase(TRAP)staining.Then,JAK signaling pathway inhibitor(AG490),AKT signaling pathway inhibitor(LY294002)and JNK signaling pathway inhibitor(SP600125)were used to evaluate the effects of IL-7 on bone solubility related active genes and protein secretion of osteoclasts by RT-PCR and ELISA,respectively.Western blot was used to explore the molecular mechanism of IL-7 promoting osteoclastogenesis.Results: IL-7 could significantly increase the number of osteoclasts in the absence of nuclear factor κB ligand(RANKL).IL-7 could significantly induce the gene expression and protein secretion of osteoclast osteolytic related components,including matrix metalloproteinase-9(MMP9),cathepsin(CathK),tartrate-resistant acid phosphatase(TRAP) and calcitonin receptor(CTR).JAK(AG490)and JNK(SP600125)signaling pathway inhibitors could significantly inhibit IL-7-induced gene expression and protein secretion.IL-7 significantly induced the activation of JAK,AKT and JNK signaling proteins.Conclusion:IL-7 can induce osteoclastogenesis independent of RANKL,and its effect may be achieved by activating JAK and JNK signaling pathways.

参考文献/References:

[1] BOYLE W J,SIMONET W S,LACEY D L.Osteoclast differentiation and activation [J].Nature,2003,423(6937):337-340.
[2] EL AZREQ M A,ARSENEAULT C,BOISVERT M,et al.Cooperation between IL-7 receptor and integrin α2β1(CD49b)drives Th17-mediated bone loss[J].Journal ofImmunology,2015,195(9):4198-4209.
[3] WEITZMANN M N,CENCI S,RIFAS L,et al.Interleukin-7 stimulates osteoclast formation by up-regulating the T-cell production of soluble osteoclastogenic cytokines[J].Blood,2000,96(5):1873-1878.
[4] SIEBERT S,TSOUKAS A,ROBERTSON J,et al.Cytokines as therapeutic targets in rheumatoid arthritis and other inflammatory diseases[J].Pharmacological Reviews,2015,67(2):280-309.
[5] O'BRIEN W,FISSEL B M,MAEDA Y,et al.Receptor activator of nuclear factor kappa-B(RANK)independent osteoclast formation and bone erosion in inflammatory arthritis[J].Arthritis Rheumatol,2016,68(12):2889-2900.
[6] VAN ROON J A,HARTGRING S A,WENTING-VAN WIJK M,et al.Persistence of interleukin 7 activity and levels on tumour necrosis factor alpha blockade in patients with rheumatoid arthritis[J].Annals of the Rheumatic Diseases,2007,66(5):664-669.
[7] SHAW A T,GRAVALLESE E M.Mediators of inflammation and bone remodeling in rheumatic disease[J].Seminars in Cell & Developmental Biology,2016,49:2-10.
[8] HARTGRING S A Y,WILLIS C R,DINA A,et al.Blockade of the interleukin-7 receptor inhibits collagen-induced arthritis and is associated with reduction of T cell activity and proinflammatory mediators[J].Arthritis & Rheumatology,2014,62(9):2716-2725.
[9] KIM J H,KIM E Y,LEE B,et al.The effects of lycii radicis cortex on RANKL-induced osteoclast differentiation and activation in RAW 264.7 cells[J].International Journal of Molecular Medicine,2016,37(3):649-658.
[10] HARTGRING S A,WILLIS C R,BIJLSMA J W,et al.Interleukin-7-aggravated joint inflammation and tissue destruction in collagen-induced arthritis is associated with T-cell and B-cell activation[J].Arthritis Research & Therapy,2012,14(3):R137.
[11] DELGADOMARTIN C,MEYER L K,HUANG B J,et al.JAK/STAT pathway inhibition overcomes IL7-induced glucocorticoid resistance in a subset of human T-cell acute lymphoblastic leukemias[J].Leukemia,2017,31(12):2568-2576.
[12] MALIK A,PAL R,GUPTA S K.Interdependence of JAK-STAT and MAPK signaling pathways during EGF-mediated HTR-8/SVneo cell invasion[J].Plos One,2017,12(5):e0178269.
[13] KITTIPATARIN C,KHALED A R.Interlinking interleukin-7[J].Cytokine,2007,39(1):75-83.
[14] KIM J H,SIM J H,LEE S,SEOL M A,et al.Interleukin-7 induces osteoclast formation via STAT5,independent of receptor activator of NF-kappaB ligand[J].Front Immunol,2017,8:1376.

备注/Memo

备注/Memo:
(收稿日期:2019-03-06)基金项目:2018年重庆市科研机构绩效激励引导专项项目 (cstc2018jxjl130011)△通信作者 E-mail:yellowsubmarinexj@163.com
更新日期/Last Update: 2019-06-30