Cell Signaling
Tokyo Medical and Dental University
Takayanagi Lab.
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2008 Mori, Y., Tsuji, S., Inui, M., Sakamoto, Y., Endo, S., Ito, Y., Fujimura, S., Koga, T., Nakamura, A., Takayanagi, H., Itoi, E. and Takai, T. Inhibitory immunoglobulin-like receptors LILRB and PIR-B negatively regulate osteoclast development. J Immunol 181, 4742-4751 (2008)
Akiyama, T., Shimo, Yu., Yanai, H., Qin, J., Ohshima, D., Maruyama, Y., Asaumi, Y., Kitazawa, J., Takayanagi, H., Penninger, J. M., Matsumoto, M., Nitta, T., Takahama, Y. and Inoue, J. The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance. Immunity 29, 423-437 (2008)
Hikosaka, Y., Nitta, T., Ohigashi, I., Yano, K., Ishimaru, N., Hayashi, Y., Matsumoto, M., Matsuo, K., Penninger, J. M., Takayanagi, H., Yokota, Y., Yamada, H., Yoshikai, Y., Inoue, J., Akiyama, T. and Takahama, Y. The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator. Immunity 29, 438-450 (2008)
Shinohara, M., Koga, T., Okamoto, K., Sakaguchi, S., Arai, K., Yasuda, H., Takai T., Kodama T., Morio T., Geha, R.S., Kitamura, D., Kurosaki, T., Ellmeier W., Takayanagi, H. Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals. Cell 132, 794-806(2008)
Asagiri, M., Hirai, T., Kunigami, T., Kamano, S., Gober, HJ., Okamoto, K., Nishikawa, K., Latz, E., Golenbock, DT., Aoki, K., Ohya, K., Imai, Y., Morishita, Y., Miyazono, K., Kato, S., Saftig, P., Takayanagi, H. Cathepsin K-dependent toll-like receptor 9 signaling revealed in experimental arthritis. Science 319, 624-627(2008)

 Abstract

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Nakashima, T. and Takayanagi, H. The dynamic interplay between osteoclasts and the immune system. Arch Biochem Biophys　(Highlight Issue: Bone Remodeling) 473(2), 166-171 (2008)---Review
2007 Nakamura, T., Imai, Y., Matsumoto T., Sato, S., Takeuchi, K.,Igarashi, K., Harada, Y., Azuma, Y., Krust, A., Yamamoto, Y., Nishina, H., Takeda, S., Takayanagi, H., Metzger, D., Kanno, J., Takaoka, K., Martin, T.J., Chambon, P., Kato, S. Osteoclastic estrogen receptor alpha mediates the osteoprotective estrogen action through Fas ligand signaling. Cell 130, 811-823 (2007)
Ochi, S., Shinohara, M., Sato, K., Gober H.J., Koga, T., Kodama, T., Takai T., Miyasaka N., Takayanagi, H. Pathological role of osteoclast costimulation in arthritis-induced bone loss. Proc Natl Acad Sci USA 104, 11394-11399(2007)
Takayanagi, H.. The role of NFAT in osteoclast formation. Ann NY Acad Sci 1116:227-237 (2007)---Review
Takayanagi, H. Novel signaling pathways and therapeutic targets in osteoclasts. Adv Exp Med Biol 602, 93-96 (2007) ---Review
Takayanagi, H. Interaction between the immune system and bone metabolism: an emerging field of osteoimmunology. Proc Jpn Acad 83, 136-143(2007)----Review
Shinohara M, Takayanagi H. Novel osteoclast signaling mechanisms. Curr Osteoporos Rep 5:67-72(2007)----Review
Takayanagi, H. Osteoimmeoimmunology - shared mechanisms and crosstalk between the bone and immune systems. Nat Rev Immunol 7, 292-304(2007)----Review
Asagiri, M., Takayanagi, H. The molecular understanding of osteoclast differentiation. Bone 40, 251-264 (2007)----Review
2006 Sato, K., Suematsu, A., Nakashima, T., Takemoto-Kimura, S., Aoki, K., Morishita, Y., Asahara, H., Ohya, K., Yamaguchi, A., Takai, T., Kodama, T., Chatila, T. A., Bito, H., & Takayanagi, H. Regulation of osteoclast differentiation and function by the CaMK-CREB pathway. Nat Med 12,1410-1416(2006)
Suematsu, A., Tajiri, Y., Nakashima, T., Taka, J., Ochi, S., Oda, H., Nakamura, K., Tanaka S., and Takayanagi H. Scientific basis for the efficacy of combined use of antirheumatic drugs against bone destruction in rheumatoid arthritis. Mod Rheumatol 17, 17-23 (2007)
Negishi H, Fujita Y, Yanai H, Sakaguchi S, Ouyang X, Shinohara M, Takayanag H, Ohba Y, Taniguchi T, Honda K. Evidence for licensing of IFN-gamma-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program. Proc Natl Acad Sci USA 103, 15136-15141(2006)
Sato, K., Suematsu, A., Okamoto, K., Yamaguchi, A., Morishita, Y., Kadono, Y., Tanaka, S., Kodama, T., Akira, S., Iwakura, Y., Cua, D. J., & Takayanagi, H. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J Exp Med 203, 2673-2682(2006)
Takayanagi, H. Amazing multifunctionality of calcineurin and NFAT signaling in bone homestasis. BoneKEy-osteovision 3, 28-31(2006)
Commentary on: Winslow MM, et al. Calcineurin/NFAT signaling in osteoblasts regulates bone mass. Dev Cell 10, 771-82 (2006)----Review
Sato, K., Takayanagi, H. Osteoclasts, rheumatoid arthritis, and osteoimmunology. Curr Opin Rheumatol 18, 419-426, 2006----Review
2005 Asagiri, M., Sato, K., Usami, T., Ochi, S., Nishina, H., Yoshida, H., Morita, I., Wagner, E. F., Mak, T. W., Serfling, E., & Takayanagi, H. Autoamplification of NFATc1 expression determines its essential role in bone homeostasis. J Exp Med 202,1261-1269 (2005)
Koga, T., Matsui, Y., Asagiri, M., Kodama, T., de Crombrugghe, B., Nakashima K. & Takayanagi, H. NFAT and Osterix cooperatively regulate bone formation. Nat Med 11, 880-885 (2005)
Kim, Y., Sato, K., Asagiri, M., Morita, I., Soma, K., and Takayanagi, H. 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. J Biol Chem, 280, 32905-32913 (2005)

Lee, F.Y., Kim, D.W., Karmin, J.A., Hong, D., Chang, S.S., Fujisawa, M., Takayanagi, H., Bigliani, L.U., Blaine, T.A., and Lee, H.J. mu-calpain regulates receptor activator of NF-kappaB (RANKL)-supported osteoclastogenesis via NF-kappaB activation in RAW 264.7 cells. J Biol Chem 280, 29929-29936 (2005)
Gohda, J., Akiyama, T., Koga, T., Takayanagi, H., Tanaka, S. and Inoue, J. RANK-mediated amplification of TRAF6 signaling leads to NFATc1 induction during osteoclastogenesis. EMBO 24,790-799 (2005)
Takatsuna, H., Asagiri, M., Kubota, T., Oka, K., Osada, T., Sugiyama, C., Saito, H., Aoki, K., Ohya, K., Takayanagi, H. and Umezawa K. Inhibition of RANKL-induced osteoclastogenesis by (-)-DHMEQ, a novel NF-kappaB inhibitor, through downregulation of NFATc1. J Bone Miner Res 20, 653-662 (2005)
Takayanagi, H., Sato, K., Takaoka, A., Taniguchi, T. Interplay between interferon and other cytokine systems in bone metabolism. Immunol Rev 208, 181-193 (2005)----Review
Takayanagi, H. All Interferons are Not Equal: Specific Mechanisms of Interfering with Osteoclastogenesis. BoneKEy-osteovision 2, 24-28 (2005)
Commentary on: Coelho LF, et al. Interferon alpha and beta differentially regulate osteoclastogenesis: Role of differential induction of chemokine CXCL11 expression. Proc Natl Acad Sci USA. 102, 11917-11922 (2005)----Review
Takayanagi, H. Osteoimmunological insight into bone damage in rheumatoid arthritis. Mod Rheumatol 15, 225-231 (2005)----Review
Takayanagi, H. Inflammatory bone destruction and osteoimmunology. J Periodont Res 40, 287-293 (2005)----Review

Takayanagi, H. Mechanistic insight into osteoclast differentiation in osteoimmunology. J Mol Med 83, 170-179 (2005)----Review
Takayanagi, H., Kim, S., Koga, T. and Taniguchi, T. Stat1-mediated cytoplasmic attenuation in osteoimmunology. J Cell Biochem 94, 232-240 (2005)----Review
2004 Matsumoto, M., Kogawa, M., Wada, S., Takayanagi, H., Tsujimoto, M., Katayama, S., Hisatake, K., Nogi, Y. Essential role of p38 mitogen-activated protein kinase in cathepsin K gene expression during osteoclastogenesis through association of NFATc1 and PU.1. J Biol Chem. 279,45969-79 (2004)
Koga, T., Inui, M., Inoue, K., Kim, S., Suematsu, A., Kobayashi, E., Iwata, T., Ohnishi, H., Matozaki, T., Kodama, T., Taniguchi, T., Takayanagi, H.*, and Takai, T.* Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis. Nature 428,758-763 (2004)
*Corresponding authors
Urushibara, M.*, Takayanagi H.*, Koga, T., Kim, S., Isobe, M., Morishita, Y., Nakagawa, T., Loeffler, M., Kodama, T., Kurosawa, H., and Taniguchi, T.  The antirheumatic drug leflunomide inhibits osteoclastogenesis by interfering with receptor activator of NF-kappaB ligand-stimulated induction of nuclear factor of activated T cells c1. Arthritis Rheum 50, 794-804 (2004)
*Equal contributors
2003 Kim, S., Koga, T., Isobe, M., Kern, B. E., Yokochi, T., Chin, Y.E., Karsenty, G., Taniguchi, T., and Takayanagi, H. Stat1 functions as a cytoplasmic attenuator of Runx2 in the transcriptional program of osteoblast differentiation. Genes Dev 17, 1979-91 (2003)
2002

Takayanagi, H., Kim, S., Koga, T., Nishina, H., Isshiki, M., Yoshida, H., Saiura, A., Isobe, M., Yokochi, T., Inoue, J, Wagner, E. F., Mak, T. W., Kodama, T., and Taniguchi, T. Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell 3, 889-901(2002)
Takayanagi, H., Kim, S., Matsuo, K., Suzuki, H., Suzuki, T., Sato, K., Yokochi, T., Oda, H., Nakamura, K., Ida, N., Wagner, E. F. & Taniguchi, T. RANKL maintains bone homeostasis through c-Fos-dependent induction of IFN-beta. Nature 416, 744-49 (2002)

Nakamura, I., Kadono, Y., Takayanagi, H., Jimi, E., Miyazaki, T., Oda, H., Nakamura, K., Tanaka, S., Rodan, G. A. & Duong le, T. IL-1 regulates cytoskeletal organization in osteoclasts via TNF receptor-associated factor 6/c-Src complex. J Immunol 168, 5103-9. (2002)
Yamamoto, A., Miyazaki, T., Kadono, Y., Takayanagi, H., Miura, T., Nishina, H., Katada, T., Wakabayashi, K., Oda, H., Nakamura, K. & Tanaka, S. Possible involvement of IkB kinase 2 and MKK7 in osteoclastogenesis induced by receptor activator of nuclear factor kappaB ligand. J Bone Miner Res 17, 612-21. (2002)
Ogasawara, K., Hida, S., Weng, Y., Saiura, A., Sato, K., Takayanagi, H., Sakaguchi, S., Yokochi, T., Kodama, T., Naitoh, M., De Martino, J. A. & Taniguchi, T. Requirement of the IFN-alpha-beta induced CXCR3 chemokine signalling for CD8+ T cell activation. Genes Cells 7, 309-320 (2002)
Takayanagi, H., Kim, S., and Taniguchi, T. Signaling crosstalk between RANKL and interferons in osteoclast differentiation. Arthritis Res 4, S227-232 (2002)----Review
Takayanagi, H. How does the immune system break and protect bone? Science (on line version, 2002)----Review
80 other review articles in Japanese
2001 Sato, K., Hida, S., Takayanagi, H., Yokochi, T., Kayagaki, N., Takeda, K., Yagita, H., Okumura, K., Tanaka, N., Taniguchi, T., Ogasawara, K. Antiviral response by natural killer cells through TRAIL gene induction by IFN-alpha/beta. Eur J Immunol 31, 3138-3146 (2001)
2000 Takayanagi, H., Ogasawara, K., Hida, S., Chiba, T., Murata, S., Sato, K., Takaoka, A., Yokochi, T., Oda, H., Tanaka, K., Nakamura, K. & Taniguchi, T. T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma. Nature 408, 600-605 (2000)
Takayanagi, H., Iizuka, H., Juji, T., Nakagawa, T., Yamamoto, A., Miyazaki, T., Koshihara, Y., Oda, H., Nakamura, K., and Tanaka, S. Involvement of receptor activator of nuclear factor kappaB ligand/osteoclast differentiation factor in osteoclastogenesis from synoviocytes in rheumatoid arthritis. Arthritis Rheum 43, 259-69 (2000)
Hida, S., Ogasawara, K., Sato, K., Abe, M., Takayanagi, H., Yokochi, T., Sato, T., Hirose, S., Shirai, T., Taki, S., Taniguchi, T. CD8+ T cell-mediated skin disease in mice lacking IRF-2, the transcriptional attenuator of interferon-alpha/beta signalling. Immunity 13, 643-655(2000)
Miyazaki, T., Katagiri, H., Kanegae, Y., Takayanagi, H., Sawada, Y., Yamamoto, A., Pando, M. P., Asano, T., Verma, I. M., Oda, H., Nakamura, K., and Tanaka, S. Reciprocal role of ERK and NF-kappaB pathways in survival and activation of osteoclasts. J Cell Biol 148, 333-42 (2000)
Miyazaki, T., Takayanagi, H., Isshiki, M., Takahashi, T., Okada, M., Fukui, Y., Oda, H., Nakamura, K., Hirai, H., Kurokawa, T., and Tanaka, S. In vitro and in vivo suppression of osteoclast function by adenovirus vector-induced csk gene. J Bone Miner Res 15, 41-51 (2000)
Nakagawa, T., Tanaka, S., Suzuki, H., Takayanagi, H., Miyazaki, T., Nakamura, K., Tsuruo, T. Overexpression of csk gene suppresses tumor metastasis in vivo. Int J Cancer 88, 384-91 (2000)
1999 Takayanagi, H., Juji, T., Miyazaki, T., Iizuka, H., Takahashi, T., Isshiki, M., Okada, M., Tanaka, Y., Koshihara, Y., Oda, H., Kurokawa, T., Nakamura, K., and Tanaka, S. Suppression of arthritic bone destruction by adenovirus-mediated csk gene transfer to synoviocytes and osteoclasts. J Clin Invest 104, 137-46 (1999)
1998 Tanaka, S., Takahashi, T., Takayanagi, H., Miyazaki, T., Oda, H., Nakamura, K., Hirai, H., and Kurokawa, T. Modulation of osteoclast function by adenovirus vector-induced epidermal growth factor receptor. J Bone Miner Res 13, 1714-20 (1998)
Yoshida, T., Horiuchi, T., Sakamoto, H., Inoue, H., Takayanagi, H., Nishikawa, T., Yamamoto, S., and Koshihara, Y. Production of parathyroid hormone-related peptide by synovial fibroblasts in human osteoarthritis. FEBS Lett 433, 331-4 (1998)
1997 Takayanagi, H., Oda, H., Yamamoto, S., Kawaguchi, H., Tanaka, S., Nishikawa, T., and Koshihara, Y. A new mechanism of bone destruction in rheumatoid arthritis: synovial fibroblasts induce osteoclastogenesis. Biochem Biophys Res Commun 240, 279-86 (1997)
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