Functional analysis of the transcription factor IRF-8 in physiological bone remodeling and inflammatory bone destruction

• Project/Area Number: 20390474
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Showa University
• Principal Investigator: TAKAMI Masamichi Showa University, 歯学部, 講師 (80307058)
• Co-Investigator(Kenkyū-buntansha): KAMIJO Ryutaro 昭和大学, 歯学部, 教授 (70233939) ; TAKAYANAGI Hiroshi 東京医科歯科大学, 医歯薬学総合研究科, 教授 (20334229)
• Co-Investigator(Renkei-kenkyūsha): TAMURA Tomohiko 横浜市立大学, 医学部, 教授 (50285144) ; YAMADA Atsushi 昭和大学, 歯学部, 講師 (50407558)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000); Fiscal Year 2010: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2009: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2008: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
• Keywords: 骨 / 破骨細胞 / 炎症 / 細胞分化 / IRF-8 / RANKL / 免疫 / 遺伝子 / Toll-like receptor / 歯周病 / 歯 / 骨代謝 / 自然免疫 / 骨芽細胞 / 骨粗鬆症 / 骨破壊 / 転写因子

Research Abstract

Identification of osteoclast differentiation regulatory factors will be beneficial for understanding the mechanisms of cellular differentiation and the development of treatment methods for bone diseases. We found that a transcription factor IRF-8 plays a role of suppressing osteoclast differentiation and IRF-8 deficient mice exhibit severe osteoporosis. We also revealed molecular mechanism of the inhibitory action of IRF-8 and published the results in Nature Medicine (15 : 1066-1071, 2009). This finding will contribute to biological research and medicine including bone diseases.

Research Products

• [Journal Article] Enhancement of bone morphogenetic protein-2-induced ectopic bone formation by transforming growth factor-β1. (2011)
  • Author(s): Tachi K., Takami M., Sato, H., Mochizuki A., Zhao B., Miyamoto Y., Tsukasaki H., Inoue T., Shintani S., Koike T., Honda Y., Suzuki O., Baba K., Kamijo R.
  • Journal Title: Tissue Engineering-Part A 17(5-6) Pages: 597-606
  • Peer Reviewed
• [Journal Article] 破骨細胞分化の制御機構 (2011)
  • Author(s): 高見正道
  • Journal Title: 生化学 83(2) Pages: 110-114
  • NAID: 10029067501
  • Peer Reviewed
• [Journal Article] Enhancement of bone morphogenetic protein-2-induced ectopic bone formation by transforming growth factor-β1 (2011)
  • Author(s): Tachi, K., Takami, M., Sato, H., Mochizuki, A., Zhao, B., Miyamoto, Y., Tsukasaki, H., Inoue, T., Shintani, S., Koike, T., Honda, Y., Suzuki, O., Baba, K., Kamijo, R.
  • Journal Title: Tissue Engineering-Part A Volume: 17 Pages: 597-606
  • Peer Reviewed
• [Journal Article] 骨代謝におけるRANKLとOPGの役割 (2011)
  • Author(s): 高見正道
  • Journal Title: 骨粗鬆症治療 Volume: 10 Pages: 31-39
• [Journal Article] 破骨細胞分化の制御機構 (2011)
  • Author(s): 高見正道, 上條竜太郎
  • Journal Title: 生化学 Volume: 83 Pages: 110-114
  • NAID: 10029067501
  • Peer Reviewed
• [Journal Article] Bone morphogenetic protein 2 enhances mouse osteoclast differentiation via increased levels of receptor activator of NF-κB ligand expression in osteoblasts. (2010)
  • Author(s): Tachi K., Takami M., Zhao B., Mochizuki A., Yamada A., Miyamoto Y., Inoue T., Baba K., Kamijo R.
  • Journal Title: Cell and Tissue Research 342(2) Pages: 213-220
  • Peer Reviewed
• [Journal Article] Honokiol inhibits osteoclast differentiation and function in vitro. (2010)
  • Author(s): Hasegawa S.-I., Yonezawa T., Ahn J.-Y., Cha B.-Y., Teruya T., Takami M., Yagasaki K., Nagai K., Woo J.-T.
  • Journal Title: Biological and Pharmaceutical Bulletin 33(3) Pages: 487-492
  • NAID: 130000248103
  • Peer Reviewed
• [Journal Article] Bone morphogenetic protein 2 enhances mouse osteoclast differentiation via increased levels of receptor activator of NF-κB ligand expression in osteoblasts (2010)
  • Author(s): Tachi, K., Takami, M., Zhao, B., Mochizuki, A., Yamada, A., Miyamoto, Y., Inoue, T., Baba, K., Kamijo, R.
  • Journal Title: Cell and Tissue Research Volume: 342 Pages: 213-220
  • Peer Reviewed
• [Journal Article] Honokiol inhibits osteoclast differentiation and function in vitro (2010)
  • Author(s): Hasegawa, S.-I., Yonezawa, T., Ahn, J.-Y., Cha, B.-Y., Teruya, T., Takami, M., Yagasaki, K., Nagai, K., Woo, J.-T.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 33 Pages: 487-492
  • NAID: 130000248103
  • Peer Reviewed
• [Journal Article] Involvement of transcription factor IRF-8 in bone metastasis of cancer (2010)
  • Author(s): Takami M., Baohong Zhao, Kamijo R.
  • Journal Title: The Waksman Foundation report of researches Volume: 33 Pages: 43-47
• [Journal Article] Osteoclast differentiation induced by synthetic octacalcium phosphate through receptor activator of NF-κB ligand expression in osteoblasts. (2009)
  • Author(s): Takami M., Mochizuki A., Yamada A., Tachi K., Zhao B., Miyamoto Y., Anada T., Honda Y., Inoue, T., Nakamura M., Suzuki O., Kamijo R.
  • Journal Title: Tissue Engineering-Part A 15(12) Pages: 3991-4000
  • Peer Reviewed
• [Journal Article] Interferon regulatory factor-8 regulates bone metabolism by suppressing osteoclastogenesis. (2009)
  • Author(s): Zhao B., Takami M., Yamada A., Wang X., Koga T., Hu X., Tamura T., Ozato K., Choi Y., Ivashkiv L.B., Takayanagi H., Kamijo R.
  • Journal Title: Nature Medicine 15(9) Pages: 1066-1071
  • Peer Reviewed
• [Journal Article] Lysine-specific gingipain promotes lipopolysaccharide- and active-vitamin D3-induced osteoclast differentiation by degrading osteoprotegerin. (2009)
  • Author(s): Yasuhara R., Miyamoto Y., Takami M., Imamura T., Potempa J., Yoshimura K., Kamijo R.
  • Journal Title: Biochemical Journal 419(1) Pages: 159-166
  • Peer Reviewed
• [Journal Article] IFN-γ down-regulates Secretoglobin 3A1 gene expression. (2009)
  • Author(s): Yamada A., Suzuki D., Miyazono A., Oshima K., Kamiya A., Zhao B., Takami M., Donnelly R.P., Itabe H., Yamamoto M., Kimura S., Kamijo R.
  • Journal Title: Biochemical and Biophysical Research Communications 379(4) Pages: 964-968
  • Peer Reviewed
• [Journal Article] The light and dark side of bisphosphonates. (2009)
  • Author(s): Jimi E., Takami M., Hiraga T., Nakamura I., Urade M., Miyamoto Y.
  • Journal Title: Journal of Oral Biosciences 51(4) Pages: 177-187
  • NAID: 10027104865
  • Peer Reviewed
• [Journal Article] Osteoclast differentiation induced by synthetic octacalcium phosphate through RANKL expression in osteoblasts (2009)
  • Author(s): Takami, M., Mochizuki, A., Yamada, A., Tachi, K., Zhao, B., Miyamoto, Y., Anada, T., Honda, Y., Inoue, T., Nakamura, M., Suzuki, O., Kamijo, R.
  • Journal Title: Tissue Eng Part A 15 Pages: 3991-4000
  • Peer Reviewed
• [Journal Article] Interferon regulatory factor-8 regulates bone metabolism by suppressing osteoclastogenesis (2009)
  • Author(s): Hu, X., Tamura, T., Ozato, K., C〓
  • Journal Title: Nature Medicine 15 Pages: 1066-1071
  • Peer Reviewed
• [Journal Article] Lysine-specific gingipain promotes lipopolysaccharide- and active-vitamin D3-induced osteoclast differentiation by degrading osteoprotegerin (2009)
  • Author(s): Yasuhara, R., Miyamoto, Y., Takami, M., Imamura, T., Potempa., J, Yoshimura, K., Kamijo, R.
  • Journal Title: Biochemical Journal 419 Pages: 159-166
  • Peer Reviewed
• [Journal Article] IFN-gamma down-regulates Secretoglobin 3A1 gene expression. (2009)
  • Author(s): Yamada A, Suzuki D, Mivazono A, Oshima K, Kamiya A, Zhao B, Takami M, Donnelly RP, Itabe H, Yamamoto M, Kimura S, Kamijo R.
  • Journal Title: Biochem Biophys Res Commun 379 Pages: 964-968
  • Peer Reviewed
• [Journal Article] Lysine-specific gingipain promotes lipopolysaccharide- and active-vitamin D3-induced osteoclast differentiation by degrading osteoprotegerin. (2009)
  • Author(s): Yasuhara R, Miyamoto Y, Takami M, Imamura T, Potempa J, Yoshimura K, Kamijo R.
  • Journal Title: Biochem J. 419 Pages: 159-166
  • Peer Reviewed
• [Journal Article] The identification of an osteoclastogenesis inhibitor through the inhibition of glyoxalase I. (2008)
  • Author(s): Kawatani M., Okumura H., Honda K., Kanoh N., Muroi M., Dohmae N., Takami M., Kitagawa M., Futamura Y., Imoto, M. Osada, H.
  • Journal Title: Proceedings of the National Academy of Sciences of the USA 105(33) Pages: 11691-11696
  • Peer Reviewed
• [Journal Article] Toll-like receptorによる破骨細胞の分化制御 (2008)
  • Author(s): 高見正道
  • Journal Title: 口腔組織培養学会誌 17 Pages: 27-33
• [Journal Article] The identification of an osteoclastogenesis inhibitor through the inhibition of glyoxalase I. (2008)
  • Author(s): Kawatani M, Okumura H, Honda K, Kanoh N, Muroi M, Dohmae N, Takami M, Kitagawa M, Futamura Y, Imoto M, Osada H.
  • Journal Title: Proc Natl Acad Sci USA 105 Pages: 11691-11696
  • Peer Reviewed
• [Journal Article] Monocarboxylate transporter-1 is required for cell death in mouse chondrocytic ATDC5 cells exposed to interleukin-1□ via late-phase activation of nuclear factor □B and expression of phagocyte-type NADPH-oxidase.
  • Author(s): Yoshimura K, Miyamoto Y, Yasuhara R, Maruyama T, Akiyama T, Yamada A, Takami M., Suzawa T, Tsunawaki S, Tachikawa T, Baba K, Kamijo R
  • Journal Title: Journal of Biological Chemistry (in press)
  • Peer Reviewed
• [Presentation] 顎顔面口腔組織における神経堤由来細胞の分布とその性質 (2010)
  • Author(s): 小野美樹、高見正道、須澤徹夫、宮内知彦、山田篤、小笠原歩、綿引淳一、林美正、林竜平、西田幸二、中村雅典、馬場一美、大隅典子、槇宏太郎、上條竜太郎
  • Organizer: 第33回 分子生物学会年会 第83回日本生化学会大会 合同大会
  • Place of Presentation: トロント(カナダ)
  • Year and Date: 2010-12-07
• [Presentation] 顎顔面口腔組織に存在する神経堤由来細胞の分布および性質の解析とその細胞を用いた骨芽細胞の分化誘導 (2010)
  • Author(s): 小野美樹、高見正道、須澤徹夫、宮内知彦、綿引淳一、南保友樹、田口智博、市川雄大、馬場一美、中村雅典、上條竜太郎、槇宏太郎
  • Organizer: 第30回 昭和歯学会例会
  • Place of Presentation: 東京
  • Year and Date: 2010-12-04
• [Presentation] 顎顔面口腔組織における神経堤由来細胞の分布解析とそれを用いた骨芽細胞様細胞の分化誘導 (2010)
  • Author(s): 小野美樹、高見正道、須澤徹夫、宮内知彦、林竜平、荒田悟、細野知彦、馬場一美、中村雅典、槇宏太郎、西田幸二、大隅典子、上條竜太郎
  • Organizer: 第47回 日本口腔組織培養学会学術大会
  • Place of Presentation: 高知
  • Year and Date: 2010-11-13
• [Presentation] Carbonic anhydrase q suppresses hypertrophic differentiation of chondrocytes (2010)
  • Author(s): Maruyama T, Miyamoto Y, Yamada A, Yamamoto G, Yoshimura K, Akiyama T, Suzawa T, Takami M, Tachikawa T, Baba K, Kamijo R
  • Organizer: American society of bone and mineral research 2010 Annual Meeting
  • Place of Presentation: トロント(カナダ)
  • Year and Date: 2010-10-15
• [Presentation] RANKシグナルによる破骨細胞分化阻害因子の抑制 (2010)
  • Author(s): 高見正道
  • Organizer: 第28回日本骨代謝学会学術集会
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2010-07-23
• [Presentation] 毛胞神経堤細胞の分離とその細胞からの象牙芽細胞への分化誘導 (2010)
  • Author(s): 宮内知彦、須澤徹夫、小野美樹、山田篤、高見正道、宮本洋一、槇宏太郎、馬場一美、上條竜太郎
  • Organizer: 第28回 日本骨代謝学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-21
• [Presentation] 骨巨細胞腫における多核巨細胞発現に対するprostaglandin E2の影響 (2010)
  • Author(s): 渋谷勲、高見正道、舘慶太、上條竜太郎、出沢明
  • Organizer: 第43回 日本整形外科学会 骨・軟骨腫瘍学術集会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-15
• [Presentation] Monocarboxylate transporter-1 is involved in activation of NF-κB and expression of NOX-2 in mouse chondrocytes exposed to interleukin-1β. (2010)
  • Author(s): Yoshimura K., Miyamoto Y., Yasuhara R., Maruyama T., Akiyama T., Yamada A., Takami M., Suzawa T., Tsunawaki S., Tachikawa T., Baba K., Kamijo R
  • Organizer: The 6th international Conference on the Biology, Chemistry, and Therapeutic Application of Nitric Oxide
  • Place of Presentation: 京都
  • Year and Date: 2010-06-14
• [Presentation] Octacalcium phosphate(OCP)による破骨細胞の分化誘導機序 (2010)
  • Author(s): 高見正道,望月文子,舘慶太,山田篤,宮本洋一,本田義知,馬場一美,井上富雄,中村雅典,穴田貴久,鈴木治,上條竜太郎
  • Organizer: 昭和大学歯学部ハイテク・リサーチ・センター平成21年度研究成果発表会
  • Place of Presentation: 東京
• [Presentation] 扁平上皮癌細胞、破骨細胞およびその前駆細胞に発現するToll-like receptorの種類とその機能 (2010)
  • Author(s): 高見正道,望月文子,舘慶太,宮本阿礼,佐藤華,岡本正人,新谷悟,井上富雄,馬場一美,上條竜太郎
  • Organizer: 昭和大学歯学部口腔癌包括的研究センター平成21年度公開シンポジウム
  • Place of Presentation: 東京
• [Presentation] BMPの骨形成誘導を促進する因子の同定と骨欠損修復への応用 (2010)
  • Author(s): 高見正道
  • Organizer: 昭和大学共同研究 平成21年度研究成果発表会
  • Place of Presentation: 東京
• [Presentation] Vitamin D and innate immune system : roles of dendritic cells in autoimmune diseases including psoriasis (2009)
  • Author(s): 高見正道
  • Organizer: 日本研究皮膚科学会
  • Place of Presentation: 福岡市(福岡)
  • Year and Date: 2009-12-04
• [Presentation] 破骨細胞分化における Interferon Regulatory factor(IRF)の役割 (2009)
  • Author(s): 高見正道
  • Organizer: 破骨細胞分化における Interferon Regulatory factor(IRF)の役割
  • Place of Presentation: 東京大学(東京)
  • Year and Date: 2009-02-21
• [Presentation] 破骨細胞分化におけるInterferon Regulatory factor (IRF)の役割 (2009)
  • Author(s): 高見正道
  • Organizer: 第6回 Osteoimmunology Forum (講演)
  • Place of Presentation: 東京・東京大学
  • Year and Date: 2009-02-21
• [Presentation] 破骨細胞の分化と機能-細胞に見る免疫と骨代謝の接点- (2009)
  • Author(s): 高見正道
  • Organizer: 埼玉医科大学学術研究セミナー
  • Place of Presentation: 埼玉医科大学(埼玉)
  • Year and Date: 2009-02-02
• [Presentation] Regulation of bone homeostasis by interferon regulatory factor 8 (IRF-8). (2009)
  • Author(s): 高見正道
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜(ワークショップ)
• [Presentation] Vitamin D and innate immune system : roles of dendritic cells in autoimmune diseases including psoriasis. (2009)
  • Author(s): 高見正道
  • Organizer: The 34th Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Fukuoka, Japan(講演)
• [Presentation] Interferon regulatory factor 8 modulates bone homeostasis by suppressing osteoclast formation. (2009)
  • Author(s): Takami M, Zhao B, Yamada A, Wang X, Koga T, Hu X, Tamura T, Ozato K, Choi Y, Ivashkiv LB, Takayanagi H, Kamijo R
  • Organizer: 第26回内藤コンファレンス
  • Place of Presentation: 徳島
• [Presentation] TGF-BETA strongly enhances BMP-2-induced ectopic bone formation. (2009)
  • Author(s): Tachi K, Takami M, Sato H, Miyamoto A, Mochizuki A, Zhao B, Inoue T, Shintani S, Nakamura M, Baba K, Kamijo R
  • Organizer: American Society for Bone & Mineral Research 31^<st> Annual Meeting
  • Place of Presentation: Denver Colorado, USA
• [Presentation] 転写因子IRF-8による骨恒常性の調節 (2009)
  • Author(s): 高見正道,趙宝紅,山田篤,Wang X,古賀貴子,Hu X,田村智彦,Ozato K,Choi Y,Ivashkiv L,高柳広,上條竜太郎
  • Organizer: 昭和大学歯学部ハイテク・リサーチ・センター平成20年度研究成果発表会
  • Place of Presentation: 東京
• [Presentation] BMP-2とヘパリンは骨芽細胞を介して相乗的に破骨細胞分化を促進する (2008)
  • Author(s): 舘慶太, 高見正道, 馬場一美, 山田篤, 望月文子, 井上富雄, 上條竜太郎
  • Organizer: 日本骨代謝学会(一般演題)
  • Place of Presentation: 大阪・大阪国際会議場
  • Year and Date: 2008-10-30
• [Presentation] 破骨細胞に対するビスホスホネートの作用機序 (2008)
  • Author(s): 高見正道
  • Organizer: 第50回歯科基礎医学会学術大会総会(サテライトシンポジウム)
  • Place of Presentation: 東京・TOC有明
  • Year and Date: 2008-09-23
• [Presentation] Interferon regulatory factor 8 (IRF8)による破骨細胞分化の調節 (2008)
  • Author(s): 高見正道
  • Organizer: 第29回日本炎症・再生医学会 (シンポジウム)
  • Place of Presentation: 東京・都市センターホテル
  • Year and Date: 2008-07-07
• [Presentation] 破骨細胞分化における転写因子IRF8の役割 (2008)
  • Author(s): 高見正道
  • Organizer: 第7回松本ホーンフォーラム (講演)
  • Place of Presentation: 長野・松本歯科大学
  • Year and Date: 2008-05-09
• [Presentation] 破骨細胞に対するビスホスホネートの作用機序 (2008)
  • Author(s): 高見正道
  • Organizer: 第50回歯科基礎医学会学術大会 サテライトシンポジウム
  • Place of Presentation: 東京(シンポジウム)
• [Presentation] Interferon regulatory factor 8(IRF8)による破骨細胞分化の調節 (2008)
  • Author(s): 高見正道
  • Organizer: 第29回日本炎症・再生医学会
  • Place of Presentation: 東京(シンポジウム)
• [Presentation] 破骨細胞分化の分子メカニズム-細胞に見る免疫と骨代謝の接点- (2008)
  • Author(s): 高見正道
  • Organizer: 第28回昭和歯学会総会
  • Place of Presentation: 東京(講演)
• [Presentation] 破骨細胞分化における転写因子IRF8の役割 (2008)
  • Author(s): 高見正道
  • Organizer: 第7回松本ボーンフォーラム
  • Place of Presentation: 松本(講演)
• [Book] Principles of Bone Biology(Third Edition(共著))(Cells of Bone : Osteoclast Generation.) (2008)
  • Author(s): Takahashi N., Udagawa N., Kobayashi Y., Takami M., Suda T.
  • Publisher: Academic Press
• [Book] Principles of Bone Biology 3rd Edition (2008)
  • Author(s): Takahashi N, Udagawa N, Kobayashi Y, Takami M, Martin T, Suda T
  • Total Pages: 19
  • Publisher: Osteoclast generation
• [Remarks] ホームページ等
• [Remarks] 昭和大学歯学部口腔生化学ホームページ
  • URL: http://www10.showa-u.ac.jp/~oralbio/index.html
• [Remarks]
  • URL: http://www10.showa-u.ac.jp/~oralbio/publications.html