Hiroshi Takayanagi

Summary

Affiliation: Tokyo Medical and Dental University
Country: Japan

Publications

  1. ncbi request reprint [Cross-talk between immune and skeletal systems]
    Hiroshi Takayanagi
    Department of Immunology, Faculty of Medicine and Graduate School of Medicine, University of Tokyo
    Nihon Rinsho 60:2287-95. 2002
  2. pmc Stage-specific functions of leukemia/lymphoma-related factor (LRF) in the transcriptional control of osteoclast development
    Kaori Tsuji-Takechi
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo ku, Tokyo 113 8549, Japan
    Proc Natl Acad Sci U S A 109:2561-6. 2012
  3. doi request reprint [Bone and cartilage destruction in rheumatoid arthritis]
    Noriko Komatsu
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo Global Center of Excellence GCOE Program, International Research for Molecular Science in Teeth and Bone Diseases, Japan
    Clin Calcium 22:179-85. 2012
  4. doi request reprint [RANKL signal and osteoimmunology]
    Tomoki Nakashima
    Department of Cell Signaling, Tokyo Medical and Dental University, Japan
    Clin Calcium 21:1131-40. 2011
  5. pmc Maf promotes osteoblast differentiation in mice by mediating the age-related switch in mesenchymal cell differentiation
    Keizo Nishikawa
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo ku, Tokyo, Japan
    J Clin Invest 120:3455-65. 2010
  6. pmc Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction
    Kojiro Sato
    Department of Cell Signaling, Graduate School, and COE Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 113 8549, Japan
    J Exp Med 203:2673-82. 2006
  7. pmc Autoamplification of NFATc1 expression determines its essential role in bone homeostasis
    Masataka Asagiri
    Department of Cell Signaling, Tokyo Medical and Dental University, Japan
    J Exp Med 202:1261-9. 2005
  8. pmc Inflammation and bone destruction in arthritis: synergistic activity of immune and mesenchymal cells in joints
    Noriko Komatsu
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University Tokyo, Japan
    Front Immunol 3:77. 2012
  9. ncbi request reprint NFAT and Osterix cooperatively regulate bone formation
    Takako Koga
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Yushima 1 5 45, Bunkyo ku, Tokyo 113 8549, Japan
    Nat Med 11:880-5. 2005
  10. ncbi request reprint Osteoimmunology and the effects of the immune system on bone
    Hiroshi Takayanagi
    Department of Cell Signaling, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo, Japan
    Nat Rev Rheumatol 5:667-76. 2009

Detail Information

Publications89

  1. ncbi request reprint [Cross-talk between immune and skeletal systems]
    Hiroshi Takayanagi
    Department of Immunology, Faculty of Medicine and Graduate School of Medicine, University of Tokyo
    Nihon Rinsho 60:2287-95. 2002
    ..The better understanding of the interactions between bone and immune cells will provide further insights into the both fields...
  2. pmc Stage-specific functions of leukemia/lymphoma-related factor (LRF) in the transcriptional control of osteoclast development
    Kaori Tsuji-Takechi
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo ku, Tokyo 113 8549, Japan
    Proc Natl Acad Sci U S A 109:2561-6. 2012
    ..Thus, this study shows that LRF plays stage-specific distinct roles in osteoclast differentiation, exemplifying the delicate transcriptional regulation at work in lineage commitment...
  3. doi request reprint [Bone and cartilage destruction in rheumatoid arthritis]
    Noriko Komatsu
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo Global Center of Excellence GCOE Program, International Research for Molecular Science in Teeth and Bone Diseases, Japan
    Clin Calcium 22:179-85. 2012
    ..Thus, Th17-synovial fibroblasts interaction is considered to be a promising therapeutic target for RA...
  4. doi request reprint [RANKL signal and osteoimmunology]
    Tomoki Nakashima
    Department of Cell Signaling, Tokyo Medical and Dental University, Japan
    Clin Calcium 21:1131-40. 2011
    ....
  5. pmc Maf promotes osteoblast differentiation in mice by mediating the age-related switch in mesenchymal cell differentiation
    Keizo Nishikawa
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo ku, Tokyo, Japan
    J Clin Invest 120:3455-65. 2010
    ..This study identifies a transcriptional mechanism for an age-related switch in cell fate determination and may provide a molecular basis for novel therapeutic strategies against age-related bone diseases...
  6. pmc Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction
    Kojiro Sato
    Department of Cell Signaling, Graduate School, and COE Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 113 8549, Japan
    J Exp Med 203:2673-82. 2006
    ..Thus, Th17 is a powerful therapeutic target for the bone destruction associated with T cell activation...
  7. pmc Autoamplification of NFATc1 expression determines its essential role in bone homeostasis
    Masataka Asagiri
    Department of Cell Signaling, Tokyo Medical and Dental University, Japan
    J Exp Med 202:1261-9. 2005
    ..Thus, this study establishes that NFATc1 represents a potential therapeutic target for bone disease and reveals a mechanism that underlies the essential role of NFATc1 in bone homeostasis...
  8. pmc Inflammation and bone destruction in arthritis: synergistic activity of immune and mesenchymal cells in joints
    Noriko Komatsu
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University Tokyo, Japan
    Front Immunol 3:77. 2012
    ....
  9. ncbi request reprint NFAT and Osterix cooperatively regulate bone formation
    Takako Koga
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Yushima 1 5 45, Bunkyo ku, Tokyo 113 8549, Japan
    Nat Med 11:880-5. 2005
    ..These results may provide important insight into the management of post-transplantation osteoporosis as well as a new strategy for promoting bone regeneration in osteopenic disease...
  10. ncbi request reprint Osteoimmunology and the effects of the immune system on bone
    Hiroshi Takayanagi
    Department of Cell Signaling, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo, Japan
    Nat Rev Rheumatol 5:667-76. 2009
    ....
  11. ncbi request reprint The role of NFAT in osteoclast formation
    Hiroshi Takayanagi
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
    Ann N Y Acad Sci 1116:227-37. 2007
    ..Such advances in the understanding of the molecular mechanism of osteoclast differentiation are expected to lead to novel therapeutic approaches to bone diseases...
  12. ncbi request reprint Novel signaling pathways and therapeutic targets in osteoclasts
    Hiroshi Takayanagi
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Japan
    Adv Exp Med Biol 602:93-6. 2007
  13. ncbi request reprint Novel osteoclast signaling mechanisms
    Masahiro Shinohara
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University and COE Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Yushima 1 5 45, Bunkyo ku, Tokyo 113 8549, Japan
    Curr Osteoporos Rep 5:67-72. 2007
    ..This review summarizes recent advances in the study of signaling mechanisms of osteoclast differentiation...
  14. ncbi request reprint Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems
    Hiroshi Takayanagi
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Yushima 1 5 45, Bunkyo ku, Tokyo 113 8549, Japan
    Nat Rev Immunol 7:292-304. 2007
    ....
  15. ncbi request reprint Interplay between interferon and other cytokine systems in bone metabolism
    Hiroshi Takayanagi
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
    Immunol Rev 208:181-93. 2005
    ....
  16. doi request reprint The unexpected link between osteoclasts and the immune system
    Hiroshi Takayanagi
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Yushima 1 5 45, Bunkyo ku, Tokyo 113 8549, Japan
    Adv Exp Med Biol 658:61-8. 2010
    ..These findings will lead to a better understanding of the pathogenesis of diseases affecting both systems and may/will provide a molecular basis for novel therapeutic strategies...
  17. doi request reprint New immune connections in osteoclast formation
    Hiroshi Takayanagi
    Department of Cell Signaling, Tokyo Medical and Dental University, Tokyo, Japan
    Ann N Y Acad Sci 1192:117-23. 2010
    ..These findings will lead to a better understanding of the pathogenesis of diseases affecting both systems and will provide a molecular basis for novel therapeutic strategies...
  18. ncbi request reprint Contribution of nuclear factor of activated T cells c1 to the transcriptional control of immunoreceptor osteoclast-associated receptor but not triggering receptor expressed by myeloid cells-2 during osteoclastogenesis
    Yoonji Kim
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Tokyo 113 8549
    J Biol Chem 280:32905-13. 2005
    ..These mechanisms, possibly together with the delicate regulation of their ligands on osteoblasts, may provide the exquisite machinery for the modulation of osteoclastogenesis in the maintenance of bone homeostasis...
  19. ncbi request reprint Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts
    Hiroshi Takayanagi
    Department of Immunology, University of Tokyo, Hongo 7 3 1, Bunkyo ku, Japan
    Dev Cell 3:889-901. 2002
    ..Thus, NFATc1 may represent a master switch for regulating terminal differentiation of osteoclasts, functioning downstream of RANKL...
  20. ncbi request reprint The antirheumatic drug leflunomide inhibits osteoclastogenesis by interfering with receptor activator of NF-kappa B ligand-stimulated induction of nuclear factor of activated T cells c1
    Makoto Urushibara
    Graduate School of Medicine, University of Tokyo, Tokyo, Japan
    Arthritis Rheum 50:794-804. 2004
    ..This study was undertaken to determine whether leflunomide has a direct action on the osteoclast lineage and to gain insights into the molecular basis for the bone-protective effect of leflunomide...
  21. pmc Pathological role of osteoclast costimulation in arthritis-induced bone loss
    Sae Ochi
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Yushima 1 5 45, Bunkyo ku, Tokyo 113 8549, Japan
    Proc Natl Acad Sci U S A 104:11394-9. 2007
    ..These results establish the pathological role of costimulatory receptors for RANK in bone loss in arthritis and may provide a molecular basis for the future therapy of inflammatory diseases...
  22. doi request reprint Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals
    Masahiro Shinohara
    Department of Cell Signaling, Graduate School, Tohoku University, Seiryo machi 4 1, Aoba ku, Sendai, Miyagi 980 8575, Japan
    Cell 132:794-806. 2008
    ..Thus, this study reveals the importance of the osteoclastogenic signaling complex composed of tyrosine kinases, which may provide the molecular basis for a new therapeutic strategy...
  23. ncbi request reprint Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis
    Takako Koga
    Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7 3 1, Bunkyo ku, Tokyo 113 0033, Japan
    Nature 428:758-63. 2004
    ..These results reveal that RANKL and M-CSF are not sufficient to activate the signals required for osteoclastogenesis...
  24. pmc RANK-mediated amplification of TRAF6 signaling leads to NFATc1 induction during osteoclastogenesis
    Jin Gohda
    Division of Cellular and Molecular Biology, Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Shirokane dai, Minato ku, Tokyo, Japan
    EMBO J 24:790-9. 2005
    ..These results suggest that RANK may harbor a specific domain that amplifies TRAF6 signaling...
  25. ncbi request reprint Regulation of osteoclast differentiation and function by the CaMK-CREB pathway
    Kojiro Sato
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Japan
    Nat Med 12:1410-6. 2006
    ..This provides a molecular basis for a new therapeutic strategy for bone diseases...
  26. ncbi request reprint Evidence for osteocyte regulation of bone homeostasis through RANKL expression
    Tomoki Nakashima
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima, Bunkyo ku, Tokyo, Japan
    Nat Med 17:1231-4. 2011
    ..Furthermore, the severe osteopetrotic phenotype that we observe in mice lacking RANKL specifically in osteocytes indicates that osteocytes are the major source of RANKL in bone remodeling in vivo...
  27. ncbi request reprint Scientific basis for the efficacy of combined use of antirheumatic drugs against bone destruction in rheumatoid arthritis
    Ayako Suematsu
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University and COE Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, 1 5 45 Yushima, Tokyo 113 8549, Japan
    Mod Rheumatol 17:17-23. 2007
    ....
  28. doi request reprint IkappaBzeta regulates T(H)17 development by cooperating with ROR nuclear receptors
    Kazuo Okamoto
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan
    Nature 464:1381-5. 2010
    ..This study provides evidence for the transcriptional mechanisms underlying T(H)17 development and points to a molecular basis for a novel therapeutic strategy against autoimmune disease...
  29. doi request reprint Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis
    Noriko Komatsu
    1 Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Bunkyo ku, Tokyo, Japan 2 Japan Science and Technology Agency JST, Exploratory Research for Advanced Technology ERATO Program, Takayanagi Osteonetwork Project, Bunkyo ku, Tokyo, Japan
    Nat Med 20:62-8. 2014
    ..These findings establish the pathological importance of Foxp3 instability in the generation of pathogenic TH17 cells in autoimmunity. ..
  30. ncbi request reprint RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-beta
    Hiroshi Takayanagi
    Department of Immunology, Faculty of Medicine and Graduate School of Medicine, University of Tokyo, Hongo 7 3 1, Bunkyo ku, Tokyo 113 0033, Japan
    Nature 416:744-9. 2002
    ..Our study places the IFN-beta system in a new context, and may offer a molecular basis for the treatment of bone diseases...
  31. ncbi request reprint Inflammatory bone destruction and osteoimmunology
    Hiroshi Takayanagi
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Center of Excellence COE Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Bunkyo ku, Tokyo, Japan
    J Periodontal Res 40:287-93. 2005
    ..This interdisciplinary research field, called 'osteoimmunology', has become increasingly important for each system by itself as well as the biology linking them. The history and recent progress of this field are reviewed...
  32. doi request reprint Osteoprotection by semaphorin 3A
    Mikihito Hayashi
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima 1 5 45, Bunkyo ku, Tokyo 113 8549, Japan
    Nature 485:69-74. 2012
    ..Intravenous Sema3A administration in mice increased bone volume and expedited bone regeneration. Thus, Sema3A is a promising new therapeutic agent in bone and joint diseases...
  33. pmc Blimp1-mediated repression of negative regulators is required for osteoclast differentiation
    Keizo Nishikawa
    Department of Cell Signaling, Tokyo Medical and Dental University, Tokyo 113 8549, Japan
    Proc Natl Acad Sci U S A 107:3117-22. 2010
    ..Thus, NFATc1 choreographs the determination of cell fate in the osteoclast lineage by inducing the repression of negative regulators as well as through its effect on positive regulators...
  34. doi request reprint Cathepsin K-dependent toll-like receptor 9 signaling revealed in experimental arthritis
    Masataka Asagiri
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Tokyo 113 8549, Japan
    Science 319:624-7. 2008
    ..These results suggest that cathepsin K plays an important role in the immune system and may serve as a valid therapeutic target in autoimmune diseases...
  35. doi request reprint Suppression of bone formation by osteoclastic expression of semaphorin 4D
    Takako Negishi-Koga
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
    Nat Med 17:1473-80. 2011
    ..Notably, Sema4D-specific antibody treatment markedly prevented bone loss in a model of postmenopausal osteoporosis. Thus, Sema4D has emerged as a new therapeutic target for the discovery and development of bone-increasing drugs...
  36. ncbi request reprint [Immune and skeletal systems]
    Hiroshi Takayanagi
    Department of Cellular Physiological Chemistry, Graduate School, Center of Excellence Program, Tokyo Medical and Dental University
    Nihon Rinsho 63:87-95. 2005
  37. ncbi request reprint [Signaling mechanism in the regulation of osteoclast differentiation by the immune system]
    Hiroshi Takayanagi
    Department of Cellular Physiological Chemistry, Graduate School, Tokyo Medical and Dental University and COE Program, 1 5 45, Yushima, Bunkyo ku, Tokyo 113 8549, Japan
    Seikagaku 75:1535-40. 2003
  38. doi request reprint Vitamin E decreases bone mass by stimulating osteoclast fusion
    Koji Fujita
    Department of Orthopedic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
    Nat Med 18:589-94. 2012
    ..These results show that serum vitamin E is a determinant of bone mass through its regulation of osteoclast fusion...
  39. ncbi request reprint The dynamic interplay between osteoclasts and the immune system
    Tomoki Nakashima
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Yushima 1 5 45, Bunkyo ku, Tokyo 113 8549, Japan
    Arch Biochem Biophys 473:166-71. 2008
    ..The framework of osteoimmunology will provide a scientific basis for future therapeutic approaches to diseases related to both of these systems...
  40. ncbi request reprint [GeneChip analysis for osteoimmunology]
    Hiroshi Takayanagi
    Department of Cell Signaling, Graduate School, Center of Excellence Program, Tokyo Medical and Dental University
    Nihon Rinsho Meneki Gakkai Kaishi 28:79-85. 2005
    ..Here we summarize our recent findings in the field of osteoimmunology obtained by GeneChip...
  41. doi request reprint Osteoimmunology: crosstalk between the immune and bone systems
    Tomoki Nakashima
    Department of Cell Signaling, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo, Japan
    J Clin Immunol 29:555-67. 2009
    ..RANKL stimulates osteoclastogenesis through nuclear factor of activated T cells cytoplasmic 1 (NFATc1), which is well known as a crucial regulator of immunity...
  42. doi request reprint Rheumatoid arthritis associated with osteopetrosis
    Yuho Kadono
    Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo, 113 0033, Japan
    Mod Rheumatol 19:687-90. 2009
    ..In spite of the severe inflammation and rapid progression of cartilage destruction, the progression of bone erosion was slow in this patient...
  43. doi request reprint A unique domain in RANK is required for Gab2 and PLCgamma2 binding to establish osteoclastogenic signals
    Yuu Taguchi
    Division of Cellular and Molecular Biology, Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
    Genes Cells 14:1331-45. 2009
    ..The present study identifies HCR as a unique domain that plays a critical role in the long-term linkage between RANK and ITAM signals, providing a molecular basis for therapeutic strategies...
  44. pmc Intracellular and extracellular ATP coordinately regulate the inverse correlation between osteoclast survival and bone resorption
    Tsuyoshi Miyazaki
    Department of Geriatric Medicine, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan
    J Biol Chem 287:37808-23. 2012
    ....
  45. doi request reprint Ly49Q, an ITIM-bearing NK receptor, positively regulates osteoclast differentiation
    Mikihito Hayashi
    Department of Cell Signaling, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Yushima 1 5 45, Bunkyo ku, Tokyo 113 8549, Japan
    Biochem Biophys Res Commun 393:432-8. 2010
    ..This study provides an example in which an ITIM-bearing receptor functions as a positive regulator of osteoclast differentiation...
  46. ncbi request reprint Stat1-mediated cytoplasmic attenuation in osteoimmunology
    Hiroshi Takayanagi
    Department of Cellular Physiological Chemistry, Graduate School, Tokyo Medical and Dental University, Yushima 1 5 45, Bunkyo ku, Tokyo 113 8549, Japan
    J Cell Biochem 94:232-40. 2005
    ....
  47. doi request reprint Autoimmune arthritis: the interface between the immune system and joints
    Noriko Komatsu
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo ku, Tokyo, Japan
    Adv Immunol 115:45-71. 2012
    ..Focusing on this interaction will lead to a better understanding of the mechanism by which the systemic immune response results in local joint disorders and also helps provide a molecular basis for novel therapeutic strategies...
  48. pmc Interferon regulatory factor-8 regulates bone metabolism by suppressing osteoclastogenesis
    Baohong Zhao
    Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo, Japan
    Nat Med 15:1066-71. 2009
    ..Our results show that IRF-8 inhibits osteoclast formation under physiological and pathological conditions and suggest a model where downregulation of inhibitory factors such as IRF-8 contributes to RANKL-mediated osteoclastogenesis...
  49. ncbi request reprint The molecular understanding of osteoclast differentiation
    Masataka Asagiri
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Yushima 1 5 45, Tokyo 113 8549, Japan
    Bone 40:251-64. 2007
    ..From the clinical point of view, RANKL signaling pathway has promise as a strategy for suppressing the excessive osteoclast formation characteristic of a variety of bone diseases...
  50. doi request reprint The role of the BH3-only protein Noxa in bone homeostasis
    Erik Idrus
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima 1 5 45, Tokyo 113 8549, Japan
    Biochem Biophys Res Commun 410:620-5. 2011
    ..This study reveals Noxa to be a crucial regulator of osteoclast apoptosis, and may provide a molecular basis for a new therapeutic approach to bone diseases...
  51. ncbi request reprint [Osteoimmunology update--from bench to bedside]
    Hiroshi Takayanagi
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University
    Nihon Rinsho 67:1031-7. 2009
    ..This emerging field will be of great importance to better understand how antirheumatic drugs work and to develop new therapeutic strategies for rheumatic diseases...
  52. pmc Agonist-selected T cell development requires strong T cell receptor signaling and store-operated calcium entry
    Masatsugu Oh-hora
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, Tokyo 113 8549, Japan
    Immunity 38:881-95. 2013
    ..Thus, STIM1 and STIM2-mediated store-operated Ca2+ influx, leading to efficient activation of NFAT (nuclear factor of activated T cells), is critical for the postselection maturation of agonist-selected T cells...
  53. ncbi request reprint IL-1 regulates cytoskeletal organization in osteoclasts via TNF receptor-associated factor 6/c-Src complex
    Ichiro Nakamura
    Department of Orthopedic Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan
    J Immunol 168:5103-9. 2002
    ..Taken together, these data suggest that IL-1 signals feed into the tyrosine kinase pathways through a TRAF6-Src molecular complex, which regulates the cytoskeletal reorganization essential for osteoclast activation...
  54. doi request reprint New insights into osteoclastogenic signaling mechanisms
    Tomoki Nakashima
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima 1 5 45, Bunkyo ku, Tokyo 113 8549, Japan
    Trends Endocrinol Metab 23:582-90. 2012
    ..The context afforded by osteoimmunology will provide a scientific basis for future therapeutic approaches to diseases related to the skeletal and immune systems...
  55. doi request reprint [The regulatory mechanisms of bone metabolism by semaphorin]
    Mikihito Hayashi
    Department of Cell Signaling, Tokyo Medical and Dental University, Japan
    Clin Calcium 22:1693-9. 2012
    ..These studies provide a scientific basis for future therapeutic approaches to bone diseases...
  56. doi request reprint [Bone and calcium update; bone research update. Osteoclastogenesis and osteoimmunology]
    Tomoki Nakashima
    Department of Cell Signaling, Tokyo Medical and Dental University, Japan
    Clin Calcium 21:93-102. 2011
    ....
  57. ncbi request reprint Osteoclasts, rheumatoid arthritis, and osteoimmunology
    Kojiro Sato
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Japan
    Curr Opin Rheumatol 18:419-26. 2006
    ..This interdisciplinary field is very important to biologic research and to the treatment of diseases associated with the bone and immune systems...
  58. ncbi request reprint [Molecular mechanism of bone destruction]
    Hirotaka Inoue
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University
    Clin Calcium 19:339-46. 2009
    ..The emerging field of osteoimmunology will be of great importance not only to the better understanding of osteoclast differentiation and activation but also to the regulation of inflammation-associated bone destruction...
  59. ncbi request reprint [Osteoclast differentiation and activation]
    Hiroshi Takayanagi
    Tokyo Medical and Dental University, Graduate School, Department of Cell Signaling
    Clin Calcium 17:484-92. 2007
    ..Here we summarize the current understanding of osteoclast differentiation and activation in the context of osteoimmunology...
  60. ncbi request reprint Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts
    Takashi Nakamura
    Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi 1 1 1, Bunkyo ku, Tokyo 113 0032, Japan
    Cell 130:811-23. 2007
    ..Our results support a model in which estrogen regulates the life span of mature osteoclasts via the induction of the Fas/FasL system, thereby providing an explanation for the osteoprotective function of estrogen as well as SERMs...
  61. doi request reprint [Animal models for bone and joint disease. Osteoimmunology and animal models for rheumatoid arthritis]
    Noriko Komatsu
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
    Clin Calcium 21:269-76. 2011
    ..Here, we summarize how various animal models for RA contributed, and can contribute to the progress in osteoimmunology and increasing understanding of RA development and treatment...
  62. doi request reprint [Regulation of bone resorption by osteocytes]
    Tomoki Nakashima
    Department of Cell Signaling, Tokyo Medical and Dental University, Japan
    Clin Calcium 22:685-96. 2012
    ..Thus, osteocytes are the commander cell at the initiation of the bone remodeling through regulation of osteoclastogenesis...
  63. ncbi request reprint Mechanistic insight into osteoclast differentiation in osteoimmunology
    Hiroshi Takayanagi
    Department of Cellular Physiological Chemistry, COE Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Graduate School, Tokyo Medical and Dental University, Japan
    J Mol Med (Berl) 83:170-9. 2005
    ..Here we summarize recent advances in the study of signaling mechanism of osteoclast differentiation in the context of osteoimmunology...
  64. ncbi request reprint [Regulation of osteoclastogenesis by activated T cells]
    Kojiro Sato
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University
    Nihon Rinsho 63:1529-32. 2005
    ..Recently, IL-17 from T cells has been reported to enhance osteoclastogenesis. Characterizing real Th subsets which support osteoclastogenesis would be beneficial to solving a clinically important problem, bone destruction in RA...
  65. doi request reprint Osteoclasts in arthritis and Th17 cell development
    Kazuo Okamoto
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
    Int Immunopharmacol 11:543-8. 2011
    ..A recent study revealed that IκBζ is essential to the development of Th17 cells. These findings comprise an important advance in our understanding of the pathogenesis of RA and potentially effective therapeutic strategies...
  66. doi request reprint Class IA phosphatidylinositol 3-kinase regulates osteoclastic bone resorption through protein kinase B-mediated vesicle transport
    Masahiro Shinohara
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
    J Bone Miner Res 27:2464-75. 2012
    ..Thus, the class IA PI3K-Akt pathway regulates the cellular machinery crucial for osteoclastic bone resorption, and may provide a molecular basis for therapeutic strategies against bone diseases...
  67. doi request reprint New regulation mechanisms of osteoclast differentiation
    Tomoki Nakashima
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
    Ann N Y Acad Sci 1240:E13-8. 2011
    ....
  68. doi request reprint Osteoclasts and the immune system
    Tomoki Nakashima
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Yushima 1 5 45, Bunkyo ku, Tokyo, 113 8549, Japan
    J Bone Miner Metab 27:519-29. 2009
    ....
  69. pmc Regulation of bone by the adaptive immune system in arthritis
    Kazuo Okamoto
    Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima 1 5 45, Bunkyo ku, Tokyo 113 8549, Japan
    Arthritis Res Ther 13:219. 2011
    ..Understanding the interaction between osteoclasts and the adaptive immune system in rheumatoid arthritis and the molecular mechanisms of Th17 development will lead to the development of potentially effective therapeutic strategies...
  70. doi request reprint Ca2+-NFATc1 signaling is an essential axis of osteoclast differentiation
    Takako Negishi-Koga
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
    Immunol Rev 231:241-56. 2009
    ..Investigation of the molecular mechanisms underlying the regulation of intracellular Ca2+ dynamics may open up new directions for therapeutic strategies in bone disease...
  71. ncbi request reprint [Introduction to osteoimmunology]
    Hiroshi Takayanagi
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University, SORST, JST
    Nihon Rinsho 63:1505-9. 2005
    ..This emerging field will be increasingly important not only for the future strategy for rheumatic diseases but also for clinical and basic studies in all the related fields...
  72. pmc Evidence for licensing of IFN-gamma-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program
    Hideo Negishi
    Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7 3 1, Bunkyo ku, Tokyo 113 0033, Japan
    Proc Natl Acad Sci U S A 103:15136-41. 2006
    ..Thus, our present study places IRF1 as an additional member participating in MyD88 signaling and provides a mechanistic insight into the enhancement of the TLR-dependent gene induction program by IFN-gamma...
  73. ncbi request reprint [Interplay between the immune and skeletal cells in the regulation of inflammatory bone destruction]
    Ayako Suematsu
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University
    Nihon Rinsho Meneki Gakkai Kaishi 30:22-8. 2007
    ..Here we summarize recent advances on the study of the regulation of cartilage and bone destruction by the immune system...
  74. pmc Roles of interleukin-6 and parathyroid hormone-related peptide in osteoclast formation associated with oral cancers: significance of interleukin-6 synthesized by stromal cells in response to cancer cells
    Kou Kayamori
    Section of Oral Pathology, Graduate School of Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, Tokyo 113 8549, Japan
    Am J Pathol 176:968-80. 2010
    ..These results indicate that OSCC provides a suitable microenvironment for osteoclast formation not only by producing IL-6 and PTHrP but also by stimulating stromal cells to synthesize IL-6...
  75. ncbi request reprint [Gene regulation network in the skeletal system]
    Hiroshi Takayanagi
    Tanpakushitsu Kakusan Koso 49:2943-9. 2004
  76. ncbi request reprint [RANKL/RANK signal transduction]
    Hiroshi Takayanagi
    Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University
    Nihon Rinsho 63:1502-4. 2005
  77. pmc Basic leucine zipper transcription factor, ATF-like (BATF) regulates epigenetically and energetically effector CD8 T-cell differentiation via Sirt1 expression
    Shoko Kuroda
    Department of Cellular Physiology and Immunology, Medical Top Track Program, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113 8510, Japan
    Proc Natl Acad Sci U S A 108:14885-9. 2011
    ..These results suggest that BATF promotes effector CD8 T-cell differentiation by regulating both epigenetic remodeling and energy metabolism through Sirt1 expression...
  78. ncbi request reprint [The regulation of osteoclastogenesis by IFN]
    Sunhwa Kim
    Department of Pathology, CBR, Harvard Medical School
    Nihon Rinsho 63:1553-61. 2005
    ..We also show the regulation of osteoblastogenesis by Stat1, an essential transcription factor for IFN signal. Our research will shed light on the novel cross-talk between IFN signals and bone cells (Table 1)...
  79. ncbi request reprint Possible involvement of IkappaB kinase 2 and MKK7 in osteoclastogenesis induced by receptor activator of nuclear factor kappaB ligand
    Aiichiro Yamamoto
    Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Japan
    J Bone Miner Res 17:612-21. 2002
    ..Either inhibition of NF-kappaB or JNK pathways dose-dependently inhibited osteoclast formation induced by RANKL. These results suggest that both NF-kappaB and JNK activation are independently required for osteoclast differentiation...
  80. ncbi request reprint mu-Calpain regulates receptor activator of NF-kappaB ligand (RANKL)-supported osteoclastogenesis via NF-kappaB activation in RAW 264.7 cells
    Francis Young In Lee
    Center for Orthopaedic Research, Department of Orthopaedic Surgery, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    J Biol Chem 280:29929-36. 2005
    ..7 cells. Taken together, our findings suggest that mu-calpain is essential to the regulation of RANKL-supported osteoclastogenesis via NF-kappaB activation...
  81. ncbi request reprint [Crosstalk between the immune and skeletal system]
    Hiroshi Takayanagi
    Ryumachi 43:624-31. 2003
  82. ncbi request reprint Essential role of p38 mitogen-activated protein kinase in cathepsin K gene expression during osteoclastogenesis through association of NFATc1 and PU.1
    Masahito Matsumoto
    Department of Molecular Biology, Saitama Medical School, Saitama, Japan
    J Biol Chem 279:45969-79. 2004
    ..These results suggest that the RANKL-induced cathepsin K gene expression is cooperatively regulated by the combination of the transcription factors and p38 MAP kinase in a gradual manner...
  83. doi request reprint The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance
    Taishin Akiyama
    Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4 6 1 Shirokane dai, Minato ku, Tokyo 108 8639, Japan
    Immunity 29:423-37. 2008
    ..These results show that developmental-stage-dependent cooperation between RANK and CD40 promotes mTEC development, thereby establishing self-tolerance...
  84. pmc Stat1 functions as a cytoplasmic attenuator of Runx2 in the transcriptional program of osteoblast differentiation
    Sunhwa Kim
    Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Tokyo 113 0033, Japan
    Genes Dev 17:1979-91. 2003
    ..Our study provides a unique example in which a latent transcription factor attenuates the activity of another transcription factor in the cytoplasm, and reveals a new regulatory mechanism in bone remodeling...
  85. ncbi request reprint Inhibition of RANKL-induced osteoclastogenesis by (-)-DHMEQ, a novel NF-kappaB inhibitor, through downregulation of NFATc1
    Hiroshi Takatsuna
    Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan
    J Bone Miner Res 20:653-62. 2005
    ..DHMEQ, a newly designed NF-kappaB inhibitor, inhibited RANKL-induced osteoclast differentiation in mouse BMMs through downregulation of the induction of NFATc1, an essential transcription factor of osteoclastogenesis...
  86. pmc Signaling crosstalk between RANKL and interferons in osteoclast differentiation
    Hiroshi Takayanagi
    Department of Immunology, Faculty of Medicine and Graduate School of Medicine, University of Tokyo, Japan
    Arthritis Res 4:S227-32. 2002
    ..Collectively, these studies revealed novel aspects of the two types of IFN, beyond their original roles in the immune response, and may offer a molecular basis for the treatment of bone diseases...
  87. doi request reprint The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator
    Yu Hikosaka
    Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima 770 8503, Japan
    Immunity 29:438-50. 2008
    ..These results indicate that RANKL produced by positively selected thymocytes is responsible for fostering thymic medulla formation, thereby establishing central tolerance...
  88. ncbi request reprint Requirement of the IFN-alpha/beta-induced CXCR3 chemokine signalling for CD8+ T cell activation
    Kouetsu Ogasawara
    Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7 3 1, Bunkyo ku, Tokyo 113 0033, Japan
    Genes Cells 7:309-20. 2002
    ..To ensure an effective immune response, distinct T cell subsets may additionally employ unique mechanism(s) for efficient activation...