Osteoimmunology and the effects of the immune system on bone

被引:366
作者
Takayanagi, Hiroshi [1 ]
机构
[1] Tokyo Med & Dent Univ, Dept Cell Signaling, Grad Sch Med & Dent Sci, Bunkyo Ku, Tokyo 1138549, Japan
基金
日本科学技术振兴机构; 日本学术振兴会;
关键词
KAPPA-B LIGAND; ANTIGEN-INDUCED ARTHRITIS; NECROSIS-FACTOR RECEPTOR; OSTEOCLAST DIFFERENTIATION; RHEUMATOID-ARTHRITIS; T-CELLS; NUCLEAR-FACTOR; CATHEPSIN-K; TERMINAL DIFFERENTIATION; OSTEOPROTEGERIN LIGAND;
D O I
10.1038/nrrheum.2009.217
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In the pathogenesis of bone destruction associated with rheumatoid arthritis, the synovium is a site of active interplay between immune and bone cells. The interaction between T cells and osteoclasts is a critical issue in the field of osteoimmunology. Accumulating evidence lends support to the theory that interleukin-17-producing T-helper cells induce the expression of receptor activator of nuclear factor kappa B ligand in synovial cells, which, together with inflammatory cytokines, stimulates the differentiation and activation of bone-resorbing osteoclasts. In addition to cellular interactions via cytokines, the immune and skeletal systems share various other molecules, including transcription factors, signaling molecules and membrane receptors. Studies of intracellular signaling mechanisms in osteoclasts have revealed that numerous immunomodulatory molecules are involved in the regulation of bone metabolism. The regulation of immune cells by bone cells is a new feature of the investigative area of osteoimmunology that implies the novel concept of the bone marrow being a crucial part of the immune system. The emerging field of osteoimmunology is important for increasing our understanding of how antirheumatic drugs (including anti-cytokine biologics) work, as well as contributing to the development of new therapeutic strategies for rheumatic diseases.
引用
收藏
页码:667 / 676
页数:10
相关论文
共 90 条
[1]   The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance [J].
Akiyama, Taishin ;
Shimo, Yusuke ;
Yanai, Hiromi ;
Qin, Junwen ;
Ohshima, Daisuke ;
Maruyama, Yuya ;
Asaumi, Yukiko ;
Kitazawa, Juli ;
Takayanagi, Hiroshi ;
Penninger, Josef M. ;
Matsumoto, Mitsuru ;
Nitta, Takeshi ;
Takahama, Yousuke ;
Inoue, Jun-ichiro .
IMMUNITY, 2008, 29 (03) :423-437
[2]   NFATc1 in mice represses osteoprotegerin during osteoclastogenesis and dissociates systemic osteopenia from inflammation in cherubism [J].
Aliprantis, Antonios O. ;
Ueki, Yasuyoshi ;
Sulyanto, Rosalyn ;
Park, Arnold ;
Sigrist, Kirsten S. ;
Sharma, Sudarshana M. ;
Ostrowski, Michael C. ;
Olsen, Bjorn R. ;
Glimcher, Laurie H. .
JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (11) :3775-3789
[3]   A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function [J].
Anderson, DM ;
Maraskovsky, E ;
Billingsley, WL ;
Dougall, WC ;
Tometsko, ME ;
Roux, ER ;
Teepe, MC ;
DuBose, RF ;
Cosman, D ;
Galibert, L .
NATURE, 1997, 390 (6656) :175-179
[4]   NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21 [J].
Arron, Joseph R. ;
Winslow, Monte M. ;
Polleri, Alberto ;
Chang, Ching-Pin ;
Wu, Hai ;
Gao, Xin ;
Neilson, Joel R. ;
Chen, Lei ;
Heit, Jeremy J. ;
Kim, Seung K. ;
Yamasaki, Nobuyuki ;
Miyakawa, Tsuyoshi ;
Francke, Uta ;
Graef, Isabella A. ;
Crabtree, Gerald R. .
NATURE, 2006, 441 (7093) :595-600
[5]   Autoamplification of NFATc1 expression determines its essential role in bone homeostasis [J].
Asagiri, M ;
Sato, K ;
Usami, T ;
Ochi, S ;
Nishina, H ;
Yoshida, H ;
Morita, I ;
Wagner, EF ;
Mak, TW ;
Serfling, E ;
Takayanagi, H .
JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 202 (09) :1261-1269
[6]   Cathepsin K-dependent Toll-like receptor 9 signaling revealed in experimental arthritis [J].
Asagiri, Masataka ;
Hirai, Toshitake ;
Kunigami, Toshihiro ;
Kamano, Shunya ;
Gober, Hans-Juergen ;
Okamoto, Kazuo ;
Nishikawa, Keizo ;
Latz, Eicke ;
Golenbock, Douglas T. ;
Aoki, Kazuhiro ;
Ohya, Keiichi ;
Imai, Yuuki ;
Morishita, Yasuyuki ;
Miyazono, Kohei ;
Kato, Shigeaki ;
Saftig, Paul ;
Takayanagi, Hiroshi .
SCIENCE, 2008, 319 (5863) :624-627
[7]   Colonic dendritic cells, intestinal inflammation, and T cell-mediated bone destruction are modulated by recombinant osteoprotegerin [J].
Ashcroft, AJ ;
Cruickshank, SM ;
Croucher, PL ;
Perry, MJ ;
Rollinson, S ;
Lippitt, JM ;
Child, JA ;
Dunstan, C ;
Felsburg, PJ ;
Morgan, GJ ;
Carding, SR .
IMMUNITY, 2003, 19 (06) :849-861
[8]   TRANCE, a tumor necrosis factor family member critical for CD40 ligand-independent T helper cell activation [J].
Bachmann, MF ;
Wong, BR ;
Josien, R ;
Steinman, RM ;
Oxenius, A ;
Choi, Y .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (07) :1025-1031
[9]   Effects of denosumab on bone mineral density and bone turnover in postmenopausal women [J].
Bone, Henry G. ;
Bolognese, Michael A. ;
Yuen, Chui Kin ;
Kendler, David L. ;
Wang, Huei ;
Liu, Yu ;
Martin, Javier San .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2008, 93 (06) :2149-2157
[10]   CHONDROCLASTS AND OSTEOCLASTS AT SUBCHONDRAL SITES OF EROSION IN THE RHEUMATOID JOINT [J].
BROMLEY, M ;
WOOLLEY, DE .
ARTHRITIS AND RHEUMATISM, 1984, 27 (09) :968-975