炎症性破骨細胞の同定とその特異的プロテアーゼに着目した骨破壊防御法の開発

• Project/Area Number: 19659099
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: 高柳 広 (2008-2009) Tokyo Medical and Dental University, 医歯学総合研究科, 教授 (20334229); 朝霧 成挙 (2007) Tokyo Medical and Dental University, 大学院・医歯学総合研究科, COE拠点形成特任講師 (20372435)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥3,200,000 (Direct Cost: ¥3,200,000); Fiscal Year 2009: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 2008: ¥1,400,000 (Direct Cost: ¥1,400,000); Fiscal Year 2007: ¥900,000 (Direct Cost: ¥900,000)
• Keywords: 自己免疫 / 関節リウマチ / カテプシン / Toll-like receptor(TLR) / プロテアーゼ / 樹状細胞 / Th17細胞 / IκBζ / 自然免疫 / Toll-like receptor (TLR) / サイトカイン

Research Abstract

1.LPS刺激により炎症性破骨細胞(iOC)においてIκBζの発現誘導が認められたため、レトロウイルスベクターを用いたRNAi法や過剰発現系を用いて、破骨細胞におけるIκBζの機能解析を行った。2.炎症性骨破壊ではTh17細胞が破骨細胞誘導性T細胞として機能する。そこでTh17細胞におけるIκBζの役割についても検討したところ、Th17細胞分化に伴いIκBζの発現が誘導されることを見出した。IκBζ欠損マウス由来のT細胞では、Th17細胞分化に障害が認められ、今後IκBζを標的としたTh17細胞制御が炎症性骨破壊治療に有効であることを明らかにし、これを報告した(11.研究発表の岡本一男らによる研究成果)。3.樹状細胞でのTLR9シグナルに対するカテプシンK阻害剤の作用機序について検討した。TLR9下流のERK、NF-κB、IRFの活性化は全てカテプシンK阻害剤によって抑えられた。一方、二重標識したTLR9を用いた蛍光共鳴エネルギー転移解析から、CpG刺激によるTLR9の立体構造変化はカテプシンK阻害剤による影響を受けないことが分かり、カテプシンK阻害剤はTLR9下流直下の活性化機序に作用することが示された。4.カテプシンK阻害剤と異なり、アポトーシスを引き起こす効果を持つビスフォスフォネート製剤はiOCに対して抑制効果が低い。iOCを用いた遺伝子発現プロファイルから、抗アポトーシス分子・Bcl-2の高発現がiOCのアポトーシス抵抗性獲得の原因であることが示唆された。このようなiOCの特性を考慮に入れた治療法が炎症性骨破壊治療に必要であることを明らかにした。

Research Products

• [Journal Article] Roles of IL-6 and PTHrP in osteoclast formation associated with oral cancers : The significance of IL-6 synthesized by stromal cells in response to cancer cells. (2010)
  • Author(s): 栢森高
  • Journal Title: American Journal of Pathology 176 Pages: 968-80
  • Peer Reviewed
• [Journal Article] The unexpected link between osteoclasts and the immune system (2010)
  • Author(s): 高柳広
  • Journal Title: Advances in Experimental Medicine and Biology(Review) 658 Pages: 61-68
• [Journal Article] Blimp1-mediated repression of negative regulators is required for osteoclast differentiation. (2010)
  • Author(s): 西川恵三
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America 16 Pages: 3117-3122
  • Peer Reviewed
• [Journal Article] Ly49Q, an ITIM-bearing NK receptor, positively regulates osteoclast differentiation (2010)
  • Author(s): 林幹人
  • Journal Title: Biochemical and Biophysical Research Communications 393 Pages: 432-438
  • Peer Reviewed
• [Journal Article] IκBζ regulates T_H17 development by cooperating with ROR nuclear receptors (2010)
  • Author(s): 岡本一男
  • Journal Title: Nature 464 Pages: 1381-1385
  • Peer Reviewed
• [Journal Article] Osteoclasts and the immune systems (2009)
  • Author(s): 中島友紀
  • Journal Title: Journal of Bone and Mineral Metabolism(Review) 27 Pages: 519-529
• [Journal Article] Osteoimmunology : crosstalk between the immune and bone systems (2009)
  • Author(s): 中島友紀
  • Journal Title: Journal of Clinical Immunology(Review) 29 Pages: 555-567
• [Journal Article] Rheumatoid arthritis associated with osteopetrosis (2009)
  • Author(s): 門野夕峰
  • Journal Title: Modern Rheumatology 19 Pages: 687-90
  • Peer Reviewed
• [Journal Article] NFATc1 Mediates Toll-Like Receptor-Independent Innate Immune Responses during Trypanosoma cruzi Indection (2009)
  • Author(s): 香山尚子
  • Journal Title: PLoS Pathogens 5
  • Peer Reviewed
• [Journal Article] Mysteries in Ca^<2+> Signaling During Osteoclast Differentiation (2009)
  • Author(s): 古賀貴子
  • Journal Title: IBMS BoneKEy Pages: 301-306
• [Journal Article] Interferon Regulatory Factor-8 Regulates Bone Metabolism by Suppressing Osteoclastogenesis. (2009)
  • Author(s): Baohong Zhao
  • Journal Title: Nature Medicine 15 Pages: 1066-1071
  • Peer Reviewed
• [Journal Article] Ca^<2+>-NFATc1 signaling is an essential axis of osteoclast differentiation (2009)
  • Author(s): 古賀貴子
  • Journal Title: Immunological Reviews(Review) 231 Pages: 241-256
• [Journal Article] The interactions and shared mechanisms of T cells and osteoclasts (2009)
  • Author(s): Hans-Juergen Gober
  • Journal Title: Inflammation and Regeneration(Review) 29 Pages: 239-248
• [Journal Article] Osteoimmunology and the effects of the immune system on bone (2009)
  • Author(s): 高柳広
  • Journal Title: Nature Reviews Rheumatology(Review) 5 Pages: 667-76
• [Journal Article] A unique domain in RANK is required for Gab2 and PLCgamma2 bindiine to establish osteoclastogenic signals (2009)
  • Author(s): 田口祐
  • Journal Title: Genes to Cells 14 Pages: 1331-1345
  • Peer Reviewed
• [Journal Article] 破骨細胞分化を司る免疫制御分子ネットワーク (2009)
  • Author(s): 篠原正浩
  • Journal Title: 実験医学 27 Pages: 852-859
• [Journal Article] 概論 骨と免疫の不可分な関係に立脚した新たな生体理解 (2009)
  • Author(s): 高柳広
  • Journal Title: 実験医学 27 Pages: 846-851
• [Journal Article] 骨免疫学のアップデート-臨床への展開- (2009)
  • Author(s): 高柳広
  • Journal Title: 日本臨床 67 Pages: 1031-1037
• [Journal Article] 破骨細胞分化決定の分子メカニズムと骨免疫学 (2009)
  • Author(s): 高柳広
  • Journal Title: 臨床血液 50 Pages: 447-452
  • NAID: 10024960212
• [Journal Article] 骨破壊制御の新たなアプローチ (2009)
  • Author(s): 中島友紀
  • Journal Title: 医薬ジャーナル社 45 Pages: 87-92
• [Journal Article] 自己免疫性関節炎とカテプシンKの関連を探る (2009)
  • Author(s): 岡本一男
  • Journal Title: 分子リウマチ治療 2 Pages: 13-18
• [Journal Article] Overview-Osteoimmunology- (2009)
  • Author(s): 高柳広
  • Journal Title: THE BONE 23 Pages: 25-29
• [Journal Article] 特集 骨・軟骨疾患の分子医学(3)Osteoimmunologyの現状と展望 (2009)
  • Author(s): 高柳広
  • Journal Title: Bio Clinica 25 Pages: 25-31
• [Journal Article] Inhibitorjr immuno globulin-like receptors LILRB and PIR-B negativelv regulate osteoclast development. (2008)
  • Author(s): Mori, Y., et al.
  • Journal Title: J Immunol 181 Pages: 4742-4751
  • Peer Reviewed
• [Journal Article] The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance. (2008)
  • Author(s): Akiyama, T., et al.
  • Journal Title: Immunity 29 Pages: 438-450
  • Peer Reviewed
• [Journal Article] The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator. (2008)
  • Author(s): Hikosaka. Y., et al.
  • Journal Title: Immunity 29 Pages: 438-450
  • Peer Reviewed
• [Journal Article] Tyrosine kinases Btk and Tec regulate osteoclast differentiationby linking RANK and ITAM signals. (2008)
  • Author(s): Shinohara, M., et al.
  • Journal Title: Cell 132 Pages: 794-806
  • Peer Reviewed
• [Journal Article] Cathepsin K-dependent toll-like receptor 9 signaling revealed in experimental arthritis. (2008)
  • Author(s): Asagiri, M., et al.
  • Journal Title: Science 319 Pages: 624-627
  • Peer Reviewed
• [Journal Article] The dynamic interplay between osteoclasts and the immune system. (2008)
  • Author(s): Nakashima, T., et al.
  • Journal Title: Arch Biochem Biophys (Highlight Issue : Bone Remodeling) 473 Pages: 166-171
  • Peer Reviewed
• [Journal Article] 自己免疫疾患にかかわるcathepsin Kの新たな役割 (2008)
  • Author(s): 岡本一男, 他
  • Journal Title: 実験医学 26 Pages: 182-187
• [Journal Article] 破骨細胞分化制御と骨免疫学 (2008)
  • Author(s): 高柳広
  • Journal Title: 最新医学 63 Pages: 2176-2181
• [Journal Article] 自己免疫性炎症におけるカテプシンKとToll-like receptor9の役割 (2008)
  • Author(s): 國上敏浩, 他
  • Journal Title: 内分泌・糖尿病科 27 Pages: 264-269
• [Journal Article] 骨免疫学研究の歴史とup to date (2008)
  • Author(s): 古賀貴子, 他
  • Journal Title: リウマチ科 40 Pages: 105-111
• [Journal Article] 破骨細胞分化シグナルと骨免疫学(第18回婦人科骨粗程症研究会、特別講演I) (2008)
  • Author(s): 高柳広
  • Journal Title: Osteoporosis Japan 16 Pages: 446-455
• [Journal Article] 炎症性骨破壊におけるThl7細胞の役割-Th17細胞による破骨細胞制御のメカニズム (2008)
  • Author(s): 岡本一男, 他
  • Journal Title: 医学のあゆみ 226 Pages: 291-294
• [Journal Article] 関節破壊のメカニズム (2008)
  • Author(s): 高柳広
  • Journal Title: 整形外科 59 Pages: 850-854
• [Journal Article] 骨免疫学の最先端 (2008)
  • Author(s): 中島友紀, 他
  • Journal Title: Mebio 25 Pages: 24-35
• [Journal Article] 免疫と骨 : 骨免疫学Osteoimmunologyの幕開け (2008)
  • Author(s): 林幹人, 他
  • Journal Title: 臨床検査 52 Pages: 556-560
• [Journal Article] 骨免疫学 (2008)
  • Author(s): 高柳広
  • Journal Title: The BONE 22 Pages: 57-61
• [Journal Article] 破骨細胞形成のメカニズムー新たな骨破壊疾患治療法の可能性 (2008)
  • Author(s): 篠原正浩, 他
  • Journal Title: DENTAL DIAMOND 33 Pages: 68-71
• [Journal Article] Osteoimmunologyと破骨細胞 (2008)
  • Author(s): 高柳広
  • Journal Title: 医学部のあゆみ 別冊 骨粗鬆症-臨床と研究の最新動向 Pages: 37-45
• [Journal Article] 関節リウマチ骨破壊のメカニズムと骨免疫学(第8回日本リウマチ財団中国・四国リウマチ外科セミナー記録集) (2008)
  • Author(s): 高柳広
  • Journal Title: Pharia Medica 26 Pages: 27-31
• [Journal Article] Cathepsin K-Dependent Toll-like Receptor 9 Signaling Revealed in Experimental Arthritis (2008)
  • Author(s): 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.
  • Journal Title: Science 319 Pages: 624-627
  • Peer Reviewed
• [Journal Article] NFAT機能の骨免疫学的考察 (2007)
  • Author(s): 朝霧成挙, 高柳広
  • Journal Title: 骨・関節・靱帯 20 Pages: 781-788
• [Presentation] Mechanism of osteoclast differentiation (2010)
  • Author(s): 高柳広
  • Organizer: 14th International Congress of Endocrinology ICE2010JES-Sponsored Symposia、第83回日本内分泌学会学術総会
  • Place of Presentation: 京都
  • Year and Date: 2010-03-29
• [Presentation] Osteoimmunology (2010)
  • Author(s): 高柳広
  • Organizer: 第30回東北免疫研究会 特別講演
  • Place of Presentation: 宮城
  • Year and Date: 2010-03-19
• [Presentation] 骨免疫学とオステオネットワーク (2010)
  • Author(s): 高柳広
  • Organizer: 第9回日本再生医療学会総会 ランチョンセミナー
  • Place of Presentation: 広島
  • Year and Date: 2010-03-18
• [Presentation] 作用機序「カテプシンKとTLR9シグナル活性化」 (2010)
  • Author(s): 高柳広
  • Organizer: NC-2300基礎研究会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-13
• [Presentation] Different Ca^<2+> sensitivity of the development of T-lineage cells. (2010)
  • Author(s): Oh-hora, M., 高柳広, Rao, A.
  • Organizer: Keystone Symposia(poster)
  • Place of Presentation: Colorado U.S.A.
  • Year and Date: 2010-02-27
• [Presentation] 骨代謝と免疫学の接点 (2010)
  • Author(s): 高柳広
  • Organizer: 第52回分子生命科学セミナー
  • Place of Presentation: 佐賀
  • Year and Date: 2010-02-19
• [Presentation] 破骨細胞分化における正と負のシグナルのバランス維持機構 (2010)
  • Author(s): 高柳広
  • Organizer: 松本歯科大学 大学院セミナー
  • Place of Presentation: 長野
  • Year and Date: 2010-02-12
• [Presentation] リウマチにおける新たなサイトカインについて (2009)
  • Author(s): 高柳広
  • Organizer: 第32回日本分子生物学会 リウマチサイトカイン研究会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-11
• [Presentation] Bone destruction in arthritis and osteoimmunology (2009)
  • Author(s): 高柳広
  • Organizer: Rheumatology Association, R.O.C.(Taiwan)
  • Place of Presentation: Yilan, Taiwan
  • Year and Date: 2009-12-06
• [Presentation] Osteoimmunologyの最先端 (2009)
  • Author(s): 高柳広
  • Organizer: 第37回日本臨床免疫学会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-11-14
• [Presentation] RANK Ligand and Osteoimmunology (2009)
  • Author(s): 高柳広
  • Organizer: 第26回内藤コンファレンス
  • Place of Presentation: 淡路
  • Year and Date: 2009-11-07
• [Presentation] Identification of novel genes regulated by NFATc1 in osteoclastogenesis (2009)
  • Author(s): 中島友紀、林幹人、高柳広
  • Organizer: 第26回内藤コンファレンス(ポスター)
  • Place of Presentation: 淡路
  • Year and Date: 2009-11-05
• [Presentation] Molecular Mechanisms of Monocyte Lineage Commitment and Function (2009)
  • Author(s): 高柳広
  • Organizer: ACR/ARHP Scientific Meeting
  • Place of Presentation: Philadelphia, U.S.A.
  • Year and Date: 2009-10-18
• [Presentation] 関節リウマチにおける骨破壊とRANKL (2009)
  • Author(s): 高柳広
  • Organizer: 第34回東京都リウマチ膠原病懇話会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-03
• [Presentation] Beckman Research Institute of the City of Hope, Division of Hematopietic Stem Cell and Leukemia Research (2009)
  • Author(s): 高柳広
  • Organizer: Osteoimmunology-interaction between bone and the immune system
  • Place of Presentation: Los Angeles, U.S.A.
  • Year and Date: 2009-09-09
• [Presentation] Fcγ Receptors Control Bone Homeostasis by Regulating Costimulation Signals in Osteoclast Lineage Cells (2009)
  • Author(s): Hans-Jurgen Gober、古賀貴子、高柳広
  • Organizer: 第27回日本骨代謝学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-07-25
• [Presentation] 破骨細胞と骨免疫学 (2009)
  • Author(s): 高柳広
  • Organizer: 第27回日本骨代謝学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-07-24
• [Presentation] New immune regulator of bone (2009)
  • Author(s): 高柳広
  • Organizer: The Bone & Teeth Gordon Research Conference
  • Place of Presentation: Maine, U.S.A.
  • Year and Date: 2009-07-15
• [Presentation] Anti-Osteoclast Therapy for Bone Destruction in Inflammation (2009)
  • Author(s): 高柳広
  • Organizer: The 9^<th> World Congress on Inflammation
  • Place of Presentation: Tokyo
  • Year and Date: 2009-07-10
• [Presentation] TNF-α and Bone Destruction in Arthritis-from the Viewpoint of Basic Research- (2009)
  • Author(s): 高柳広
  • Organizer: The 9^<th> World Congress on Inflammation
  • Place of Presentation: Tokyo
  • Year and Date: 2009-07-08
• [Presentation] Immune Regulation of Osteoclastogenesis (2009)
  • Author(s): 高柳広
  • Organizer: The 3^<rd> Global COE International Symposium, Tokyo Medical and Dental University
  • Place of Presentation: Tokyo
  • Year and Date: 2009-06-10
• [Presentation] 関節リウマチの骨破壊とIL-6 (2009)
  • Author(s): 高柳広
  • Organizer: 第82回日本整形外科学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2009-05-17
• [Presentation] RANKL Signaling and Osteoimmunology (2009)
  • Author(s): 高柳広
  • Organizer: The 66^<th> KSBMB Annual Meeting, World Trade Center
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2009-05-13
• [Presentation] New Immune Connections During Osteoclatogenesis (2009)
  • Author(s): 高柳広
  • Organizer: The 3^<rd> New York Skeletal Biology and Medicine Conference, Mount Sinai School of Medicine
  • Place of Presentation: New York, U.S.A.
  • Year and Date: 2009-04-30
• [Presentation] 関節リウマチ骨破壊への新たなアプローチ (2009)
  • Author(s): 高柳広
  • Organizer: 第53回日本リウマチ学会総会・学術集会、第18回国際リウマチシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2009-04-23
• [Presentation] 関節リウマチ骨破壊と骨免疫学 (2009)
  • Author(s): 高柳広
  • Organizer: 第37回九州リウマチ学会イブニングセミナー
  • Place of Presentation: 長崎
  • Year and Date: 2009-03-14
• [Presentation] 関節リウマチ骨破壊と骨免疫学 (2009)
  • Author(s): 高柳広
  • Organizer: 兵庫県リウマチ医の会
  • Place of Presentation: 兵庫
  • Year and Date: 2009-03-07
• [Presentation] Osteoimmunology-Interact ions and shared mechanisms between theimmune system and bone. (2009)
  • Author(s): Takayanagi, H.
  • Organizer: The Annual Symposium of IFReC (Immunology Frontier Research Center), Osaka University
  • Place of Presentation: Osaka
  • Year and Date: 2009-02-12
• [Presentation] 炎症性骨破壊と骨免疫学 (2009)
  • Author(s): 高柳広
  • Organizer: 第32回皮膚脈管膠原病研究会
  • Place of Presentation: 京都
  • Year and Date: 2009-01-23
• [Presentation] 関節リウマチの骨破壊と骨免疫学 (2009)
  • Author(s): 高柳広
  • Organizer: 山口県整形外科医会
  • Place of Presentation: 山口
  • Year and Date: 2009-01-17
• [Presentation] 運動器疾患の分子ネットワークの解明と治療応用 (2009)
  • Author(s): 高柳広
  • Organizer: ゲノムネットワークプロジェクト公開シンポジウム「ゲノムネットワークが拓く新しい医学・生物学」
  • Place of Presentation: 東京
  • Year and Date: 2009-01-16
• [Presentation] 骨免疫学研究の現状・課題・展望 (2009)
  • Author(s): 高柳広
  • Organizer: 第29回コスモ・バイオ バイオプロダクトセミナー
  • Place of Presentation: 東京、大阪
• [Presentation] 加齢に伴い発現変動する転写因子Mafの細胞分化に及ぼす影響 (2008)
  • Author(s): 西川恵三, 他
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] Tecファミy ーチロシンキナーゼによる破骨細胞分化制御 (2008)
  • Author(s): 古賀貴子, 他
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] ERK2と相互作用するタンパク質の探索 (2008)
  • Author(s): 春宮覚, 他
  • Organizer: 第31回日本分子生物学会年会・第81回目本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] Molecular lechanisi in osteoclastogenesis (2008)
  • Author(s): Takayanagi, H.
  • Organizer: JSPS Core-to-Core Program International Workshop on Advanced Bone and Joint Science (ABJS)
  • Place of Presentation: Tokyo
  • Year and Date: 2008-12-04
• [Presentation] 関節リウマチ骨破壊と骨免疫学 (2008)
  • Author(s): 高柳広
  • Organizer: 病態代謝血管医学セミナー
  • Place of Presentation: 熊本
  • Year and Date: 2008-11-13
• [Presentation] Bone and Immune System (2008)
  • Author(s): Takayanagi, H.
  • Organizer: Annual Meeting of Korean Endocrine Society
  • Place of Presentation: Jeju, Korea
  • Year and Date: 2008-11-08
• [Presentation] 『骨免疫学の最前線」破骨細胞の新たな制御メカニズム (2008)
  • Author(s): 高柳広
  • Organizer: 第26回目本骨代謝学会学術集会ランチョンセミナー
  • Place of Presentation: 大阪
  • Year and Date: 2008-10-31
• [Presentation] RANKLと骨免疫学 (2008)
  • Author(s): 高柳広
  • Organizer: 第26回目本骨代謝学会学術集会イブニングセミナー
  • Place of Presentation: 大阪
  • Year and Date: 2008-10-30
• [Presentation] 加齢に伴う骨量減少の原因となる転写メカニズムの探索 (2008)
  • Author(s): 西川恵三, 他
  • Organizer: 第26回目本骨代謝学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2008-10-29
• [Presentation] Thl7 Cytokines and their Effects (2008)
  • Author(s): Takayanagi, H.
  • Organizer: 2008 ACR Basic Research conference
  • Place of Presentation: San Francisco
  • Year and Date: 2008-10-24
• [Presentation] カテプシンKはT01l-like receptor 9シグナルを介して自己免疫性炎症を制御する (2008)
  • Author(s): 國上敏浩, 他
  • Organizer: 第36回日本臨床免疫学会総会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-18
• [Presentation] Molecular determinant in osteoclast differentiation (2008)
  • Author(s): 高柳広
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-10
• [Presentation] 炎症性骨破壊と骨免疫学 (2008)
  • Author(s): 高柳広
  • Organizer: 第3回大阪皮膚アンチエイジング研究会
  • Place of Presentation: 大阪
  • Year and Date: 2008-10-09
• [Presentation] The crucial role of RANKL in bone loss and canser metastasis. (2008)
  • Author(s): Nakashima T., et al.
  • Organizer: The 13th Asia Pacific League of Associations for Rheumatology Congress
  • Place of Presentation: Yokohama
  • Year and Date: 2008-09-26
• [Presentation] Tec kinases form an osteoclastogenic signaling complex with SLPadaptor proteins (2008)
  • Author(s): Koga T., et al.
  • Organizer: The 13th Asia Pacific League of Associations for Rheumatology Congress
  • Place of Presentation: Yokohama
  • Year and Date: 2008-09-26
• [Presentation] Therapeutic potential of Tec kinase inhibi tors on bone destruction (2008)
  • Author(s): Arai K., et al.
  • Organizer: The 13th Asia Pacific League of Associations for Rheumatology Congress
  • Place of Presentation: Yokohama
  • Year and Date: 2008-09-26
• [Presentation] Tyrosine kinases Btk and Tec are essential for osteoclastdifferentiation (2008)
  • Author(s): Shinohara M., et al.
  • Organizer: The 13th Asia Pacific League of Associations for Rheumatology Congress
  • Place of Presentation: Yokohama
  • Year and Date: 2008-09-25
• [Presentation] A Novel Role of Cathepsin K In Autoimmunity : Regulation ofToll-Like Receptor 9 signal ing in Dendri tic Cells (2008)
  • Author(s): Okamoto M., et al.
  • Organizer: The 13th Asia Pacific League of Associations for Rheumatology Congress
  • Place of Presentation: Yokohama
  • Year and Date: 2008-09-24
• [Presentation] NFATcl-dependent program of osteoclast differentiation andfunction. (2008)
  • Author(s): Hayashi M., et al.
  • Organizer: The 13th Asia Pacific League of Associations for Rheumatology Congress
  • Place of Presentation: Yokohama
  • Year and Date: 2008-09-24
• [Presentation] Effect of combined use of anti-rheumatic drugs on osteoclastdifferentiation. (2008)
  • Author(s): Suematsu A., et al.
  • Organizer: The 13th Asia Pacific League of Associations for Rheumatology Congress
  • Place of Presentation: Yokohama
  • Year and Date: 2008-09-24
• [Presentation] Osteoclasts in Arthritis and Osteoimmunology (2008)
  • Author(s): Takayanagi, H.
  • Organizer: The 13^<th> Asia Pacific League ofAssociations for Rheumatology Congress
  • Place of Presentation: Yokohama
  • Year and Date: 2008-09-23
• [Presentation] Use of mouse genetics in bone biology and osteoimmunology. (2008)
  • Author(s): Takayanagi, H.
  • Organizer: EMBO Practice Course on "Anatomy and Embryology of the Mouse"
  • Place of Presentation: Zagreb, Croatia
  • Year and Date: 2008-09-10
• [Presentation] 新たな破骨細胞制御メカニズム (2008)
  • Author(s): 高柳広
  • Organizer: 第28回骨形態計測学会
  • Place of Presentation: 東京
  • Year and Date: 2008-07-26
• [Presentation] 関節リウマチ骨破壊と骨免疫学 (2008)
  • Author(s): 高柳広
  • Organizer: 東京骨関節フォーラム
  • Place of Presentation: 東京
  • Year and Date: 2008-07-12
• [Presentation] 免疫不全と骨代謝-Tecファミリーチロシンキナーゼによる破骨細胞分化制御- (2008)
  • Author(s): 篠原正浩, 他
  • Organizer: 第2 9回日本炎症・再生医学会
  • Place of Presentation: 東京
  • Year and Date: 2008-07-10
• [Presentation] 関節リウマチ骨破壊と骨免疫 (2008)
  • Author(s): 高柳広
  • Organizer: 免疫シンフォニー
  • Place of Presentation: 大阪
  • Year and Date: 2008-06-28
• [Presentation] 関節リウマチ骨破壊と骨免疫学 (2008)
  • Author(s): 高柳広
  • Organizer: 城北関節炎・ RA ・ OA ・ AS談話会
  • Place of Presentation: 東京
  • Year and Date: 2008-06-26
• [Presentation] The role of Tec family kinases in osteoclast different iation (2008)
  • Author(s): Shinohara M., Gt al.
  • Organizer: 2nd International Conference on Osteoimmunology : Interactions of the Immune and Skeletal Systems
  • Place of Presentation: Rhodos, Greece
  • Year and Date: 2008-06-13
• [Presentation] Cathepsin K regulated TH17 cell polarization through toll-likereceptor 9 signal ing in dendritic cells (2008)
  • Author(s): Gober H. J., et al.
  • Organizer: 2nd International Conference on Osteoimmunology : Interactions of the Immune and Skeletal Systems
  • Place of Presentation: Rhodos, Greece
  • Year and Date: 2008-06-13
• [Presentation] Unexpected link between osteoclast and the immune system (2008)
  • Author(s): Takayanagi, H.
  • Organizer: 2nd International Conference on Osteoimmunology : Inter act ions of the Immune and Skeletal Systems
  • Place of Presentation: Rhodos, Greece
  • Year and Date: 2008-06-11
• [Presentation] (2008)
  • Author(s): 高柳広
  • Organizer: 第86回膠原病研究会
  • Place of Presentation: 新潟
  • Year and Date: 2008-06-03
• [Presentation] 関節リウマチ骨破壊と骨免疫学 (2008)
  • Author(s): 高柳広
  • Organizer: 埼玉医大整形同門会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-31
• [Presentation] 関節リウマチの骨破壊と骨免疫学 (2008)
  • Author(s): 高柳広
  • Organizer: 第81回日本整形外科学会教育研修講演
  • Place of Presentation: 札幌
  • Year and Date: 2008-05-22
• [Presentation] Tecファミリーキナーゼによる破骨細胞分化制御機構(The role of Tec family kinases in osteoclast differentiation) (2008)
  • Author(s): 篠原正浩, 他
  • Organizer: 第52回日本リウマチ学会総会・学術集会ワークショップ32「骨代謝と骨粗鬆症」
  • Place of Presentation: 札幌
  • Year and Date: 2008-04-23
• [Presentation] 破骨細胞の新たな制御メカニズム (2008)
  • Author(s): 高柳広
  • Organizer: 第52回目本リウマチ学会総会・学術集会シンポジウム「関節リウマチ病態解明のトピックス」
  • Place of Presentation: 札幌
  • Year and Date: 2008-04-23
• [Presentation] カテプシンKはToll様受容体9シグナルを介して自己免疫性炎症疾患の重症度を決定する (2008)
  • Author(s): 朝霧成挙, 他
  • Organizer: 第52回目本リウマチ学会総会・学術集会ワークショップ9「関節リウマチの病因・病態1」
  • Place of Presentation: 札幌
  • Year and Date: 2008-04-22
• [Presentation] サイトカインと骨破壊 (2008)
  • Author(s): 高柳広
  • Organizer: 第52回日本リウマチ学会総会・学術集会イブニングセミナー
  • Place of Presentation: 札幌
  • Year and Date: 2008-04-22
• [Presentation] 骨溶解酵素カテプシンKはTLR9信号を制御して 自己免疫性炎症疾患の重症度を決定する (2008)
  • Author(s): 朝霧成挙
  • Organizer: 第2回 Bone Research Seminar
  • Place of Presentation: 丸ビル(東京)
  • Year and Date: 2008-02-29
• [Presentation] Osteoclast-Independent Function of Cathepsin K : Regulation ofToll-like Receptor 9 Signaling in Autoimmunity. (2008)
  • Author(s): Okamoto, K., et al.
  • Organizer: The 30th Annual Meeting of the AmericanSociety for Bone and Mineral Research.
  • Place of Presentation: Montreal. Canada
• [Presentation] Tec Rinases, Therapeutic Targets for Bone Destructive Diseases. (2008)
  • Author(s): Shinohara M., et al.
  • Organizer: The 30th Annual Meeting of the AmericanSociety for Bone and Mineral Research.
  • Place of Presentation: Montreal, Canada
• [Presentation] Targeting Cathepsin K in autoimmune arthritis reveals its function in dendritic cells (2007)
  • Author(s): ASAGIRI Masataka, HIRAI Toshitake, KUNIGAMI Toshihiro, KAMANO Shunya, GOBER Hans-Juergen, OKAMOTO Kazuo, NISHIKAWA Keizo, MORISHITA Yasuyuki, TAKAYANAGI Hiroshi
  • Organizer: 第36回日本免疫学会総会・学術集会
  • Place of Presentation: 品川プリンスホテル(東京)
  • Year and Date: 2007-11-22
• [Book] 9 : Cytokine and Growth Factor Regulation of Osteoclastogenesis (2009)
  • Author(s): 高柳広
  • Total Pages: 13
  • Publisher: Cold Spring Harbor Laboratory Press The Skeletal System
• [Book] 炎症・再生医学事典 5.骨・関節-b.破骨細胞 (2009)
  • Author(s): 高柳広
  • Total Pages: 4
  • Publisher: 朝倉書店
• [Remarks]
  • URL: http://osteoimmunology.com/
• [Remarks]
  • URL: http://osteoimmunology.com/
• [Remarks]
  • URL: http://osteoimmunology.com/
• [Patent(Industrial Property Rights)] カテプシン阻害剤を有効成分として含有するToll様受容体のシグナル伝達の調整剤 (2008)
  • Inventor(s): 高柳広、朝霧成挙、平井利武、
  • Industrial Property Rights Holder: 国立大学法人東京医科歯科大学、日本ケミファ株式会社
  • Filing Date: 2008-10-24
• [Patent(Industrial Property Rights)] カテプシン阻害剤を有効成分として含有するTo11様受容体のシグナル伝達の調整剤 (2007)
  • Inventor(s): 高柳広, 朝霧成挙, 平井利武
  • Industrial Property Rights Holder: 国立大学法人 東京医科歯科大学, 日本ケミフア株式会
  • Filing Date: 2007