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

2010 Fiscal Year Final Research Report

• 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
• Keywords: 骨 / 破骨細胞 / 炎症 / 細胞分化 / IRF-8 / RANKL / 炎症 / 免疫 / 遺伝子 / Toll-like receptor / 歯周病 / 歯

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
  • 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
  • Peer Reviewed
• [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
  • 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] 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] 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
  • Year and Date: 20100300
• [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
  • Year and Date: 20100300
• [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
  • Year and Date: 20100300
• [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)
  • Year and Date: 20091200
• [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)
  • Year and Date: 20091200
• [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
  • Year and Date: 20091100
• [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
  • Year and Date: 20090900
• [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
  • Year and Date: 20090300
• [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)
  • Year and Date: 20080900
• [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)
  • Year and Date: 20080700
• [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)
  • Year and Date: 20080600
• [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)
  • Year and Date: 20080500
• [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.
  • Total Pages: 173-190
  • Publisher: Academic Press
• [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