Interleukin-7 Induces Osteoclast Formation via STAT5, Independent of Receptor Activator of NF-kappaB Ligand

被引:25
作者
Kim, Jin-Hee [1 ,2 ]
Sim, Ji Hyun [1 ]
Lee, Sunkyung [1 ]
Seol, Min A. [1 ,3 ,4 ]
Ye, Sang-Kyu [3 ,4 ,5 ,6 ]
Shin, Hyun Mu [1 ,3 ,4 ,6 ]
Lee, Eun Bong [6 ,7 ]
Lee, Yun Jong [7 ]
Choi, Yun Jung [8 ,9 ]
Yoo, Wan-Hee [8 ,9 ]
Kim, Jin Hyun [10 ]
Kim, Wan-Uk [11 ]
Lee, Dong-Sup [1 ,3 ,4 ,6 ]
Kim, Jin-Hong [12 ]
Kang, Insoo [13 ]
Kang, Seong Wook [10 ]
Kim, Hang-Rae [1 ,3 ,4 ,6 ]
机构
[1] Seoul Natl Univ, Dept Anat & Cell Biol, Coll Med, Seoul, South Korea
[2] Cheongju Univ, Dept Biomed Lab Sci, Coll Hlth Sci, Cheongju, South Korea
[3] Seoul Natl Univ, Dept Biomed Sci, Coll Med, Seoul, South Korea
[4] Seoul Natl Univ, Biomed Sci Project BK21Plus, Coll Med, Seoul, South Korea
[5] Seoul Natl Univ, Dept Pharmacol, Coll Med, Seoul, South Korea
[6] Seoul Natl Univ, Med Res Inst, Coll Med, Seoul, South Korea
[7] Seoul Natl Univ, Dept Internal Med, Coll Med, Seoul, South Korea
[8] Chonbuk Natl Univ, Dept Internal Med, Med Sch, Jeonju, South Korea
[9] Chonbuk Natl Univ Hosp, Res Inst Clin Med, Jeonju, South Korea
[10] Chungnam Natl Univ, Sch Med, Dept Internal Med, Daejeon, South Korea
[11] Catholic Univ Korea, Dept Internal Med, Seoul, South Korea
[12] Seoul Natl Univ, Dept Biol Sci, Coll Nat Sci, Seoul, South Korea
[13] Yale Univ, Sch Med, Dept Internal Med, Rheumatol Sect, New Haven, CT 06510 USA
来源
FRONTIERS IN IMMUNOLOGY | 2017年 / 8卷
基金
新加坡国家研究基金会;
关键词
osteoclast; intereleukin-7; IL-7 receptor alpha; STAT5; RANKL; monocyte; TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; RHEUMATOID-ARTHRITIS; SYNOVIAL FIBROBLASTS; OSTEOPROTEGERIN LIGAND; TRANSCRIPTION FACTOR; BONE-RESORPTION; CD4+T CELLS; RANKL; IL-7;
D O I
10.3389/fimmu.2017.01376
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Interleukin-7 (IL-7), which is required for the development and survival of T cells in the thymus and periphery, plays a role in joint destruction. However, it remains unclear how IL-7 affects osteoclast formation. Thus, we investigated the mechanism by which IL-7 induced osteoclast formation through IL-7 receptor a (IL-7R alpha) in osteoclast precursors. We cultured peripheral blood mononuclear cells or synovial fluid mononuclear cells with IL-7 in the presence or absence of an appropriate inhibitor to analyze osteoclast formation. We also constructed IL-7R alpha-expressing RAW264.7 cells to uncover the mechanism(s) by which IL-7 induced osteoclast formation differed from that of receptor activator of nuclear factor.B ligand (RANKL). We found that IL-7 induced osteoclast formation of human monocytes from peripheral blood or synovial fluid in a RANKL-independent and a signal transducer and activator of transcription 5 (STAT5)-dependent manner. IL-7-induced osteoclasts had unique characteristics, such as small, multinucleated tartrate-resistant acid phosphatase positive cells and no alterations even when RANKL was added after IL-7 pretreatment. RAW264.7 cells, if overexpressing IL-7Ra, also were able to differentiate into osteoclasts by IL-7 through a STAT5 signaling pathway. Furthermore, IL-7-induced osteoclast formation was repressed by inhibitors of the IL-7R signaling molecules Janus kinase and STAT5. Our findings demonstrate that IL-7 is a truly osteoclastogenic factor, which may induce osteoclast formation via activation of STAT5, independent of RANKL. We also suggest the possibility that an IL-7R pathway blocker could alleviate joint damage by inhibiting osteoclast formation, especially in inflammatory conditions.
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页数:13
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共 46 条
[11]   Interleukin-7 induced immunopathology in arthritis [J].
Hartgring, S. A. Y. ;
Bijlsma, J. W. J. ;
Lafeber, F. P. J. G. ;
van Roon, J. A. G. .
ANNALS OF THE RHEUMATIC DISEASES, 2006, 65 :69-74
[12]   Interleukin-7-aggravated joint inflammation and tissue destruction in collagen-induced arthritis is associated with T-cell and B-cell activation [J].
Hartgring, Sarita A. Y. ;
Willis, Cynthia R. ;
Bijlsma, Johannes W. J. ;
Lafeber, Floris P. J. G. ;
van Roon, Joel A. G. .
ARTHRITIS RESEARCH & THERAPY, 2012, 14 (03)
[13]   Blockade of the Interleukin-7 Receptor Inhibits Collagen-Induced Arthritis and Is Associated With Reduction of T Cell Activity and Proinflammatory Mediators [J].
Hartgring, Sarita A. Y. ;
Willis, Cynthia R. ;
Alcorn, Dina ;
Nelson, Laurel J. ;
Bijlsma, Johannes W. J. ;
Lafeber, Floris P. J. G. ;
van Roon, Joel A. G. .
ARTHRITIS AND RHEUMATISM, 2010, 62 (09) :2716-2725
[14]   Elevated Expression of Interleukin-7 Receptor in Inflamed Joints Mediates Interleukin-7-Induced Immune Activation in Rheumatoid Arthritis [J].
Hartgring, Sarita A. Y. ;
van Roon, Joel A. G. ;
Wenting-van Wijk, Marion ;
Jacobs, Kim M. G. ;
Jahangier, Zalima N. ;
Willis, Cynthia R. ;
Bijlsma, Johannes W. J. ;
Lafeber, Floris P. J. G. .
ARTHRITIS AND RHEUMATISM, 2009, 60 (09) :2595-2605
[15]   RANKL-independent human osteoclast formation with APRIL, BAFF, NGF, IGF I and IGF II [J].
Hemingway, F. ;
Taylor, R. ;
Knowles, H. J. ;
Athanasou, N. A. .
BONE, 2011, 48 (04) :938-944
[16]   Bone resorption is regulated by cell-autonomous negative feedback loop of Stat5-Dusp axis in the osteoclast [J].
Hirose, Jun ;
Masuda, Hironari ;
Tokuyama, Naoto ;
Omata, Yasunori ;
Matsumoto, Takumi ;
Yasui, Tetsuro ;
Kadono, Yuho ;
Hennighausen, Lothar ;
Tanaka, Sakae .
JOURNAL OF EXPERIMENTAL MEDICINE, 2014, 211 (01) :153-163
[17]   Interleukin-1β and tumor necrosis factor-α, but not interleukin-6, stimulate osteoprotegerin ligand gene expression in human osteoblastic cells [J].
Hofbauer, LC ;
Lacey, DL ;
Dunstan, CR ;
Spelsberg, TC ;
Riggs, BL ;
Khosla, S .
BONE, 1999, 25 (03) :255-259
[18]   Cell biology of IL-7, a key lymphotrophin [J].
Jiang, Q ;
Li, WQ ;
Aiello, FB ;
Mazzucchelli, R ;
Asefa, B ;
Khaled, AR ;
Durum, SK .
CYTOKINE & GROWTH FACTOR REVIEWS, 2005, 16 (4-5) :513-533
[19]   Minireview: The OPG/RANKL/RANK system [J].
Khosla, S .
ENDOCRINOLOGY, 2001, 142 (12) :5050-5055
[20]   Reciprocal Activation of CD4+T Cells and Synovial Fibroblasts by Stromal Cell-Derived Factor 1 Promotes RANKL Expression and Osteoclastogenesis in Rheumatoid Arthritis [J].
Kim, Hae-Rim ;
Kim, Kyoung-Woon ;
Kim, Bo-Mi ;
Jung, Hong-Geun ;
Cho, Mi-La ;
Lee, Sang-Heon .
ARTHRITIS & RHEUMATOLOGY, 2014, 66 (03) :538-548