Molecular mechanism of a novel pathogenic factor in the periodontitis.

• Project/Area Number: 20390469
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: National Institute for Longevity Sciences,NCGG
• Principal Investigator: NIIDA Shumpei National Institute for Longevity Sciences,NCGG, 室長 (10137630)
• Co-Investigator(Renkei-kenkyūsha): MIYAUCHI Mutsumi 広島大学, 大学院・医歯薬総合研究科, 准教授 (50169265) ; SHIBAYAMA Keigo 国立感染症研究所, 部長 (50283437)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2010: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2009: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2008: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 骨破壊 / 破骨細胞 / TLR / γ-GTP / バクテリア / 破骨細胞細胞 / 歯周炎

Research Abstract

We found that bacterial gamma-glutamyl transpeptidase (bGGT) could induce osteoclast formation from the culture of bone marrow macrophages (BMMs). In the present study, we investigated the molecular mechanism of bGGT-mediated osteoclastogenesis. Because toll-like receptors (TLRs) are innate immune sensor for bacterial components, we firstly examined osteoclast induction test using BMMs derived from MyD88-deficient mice, which is a common adaptor molecule for several TLRs. The bGGT could not induce osteoclast formation in the cultures of these BMMs. To determine the bGGT specific receptor, we tested the osteoclast formation in TLR2- or TLR4-deficient BMMs. At last, we found that bGGT-dependent osteoclastogenesis did not occur in the TLR4- deficient BMMs. Furthermore, the phenotypes of signal transduction stimulated by bGGT were same as by LPS which is major ligand for TLR4. These results strongly suggest that bGGT stimulates osteoclastogenesis via TLR4.

Research Products

• [Journal Article] Rho-kinase limits FGF-2-stimukated VEGF release in osteoblasts. (2010)
  • Author(s): Natsume H, Tokuda H, Adachi S, Takai S, Matsushima-N R, Kato K, Minamitani C, Niida S, Mizutani J, Kozawa O, Otsuka T.
  • Journal Title: Bone 46(4) Pages: 1493-1497
• [Journal Article] Is structural remodeling of fibrillated atria the consequence of tissue hypoxia? (2010)
  • Author(s): Ogi H, Nakano Y, Niida S, Dote K, Hirai Y, Suenari K, Tonouchi Y, Oda N, Makita Y, Ueda S, Kajihara K, Imai K, Sueda T, Chayama K, Kihara Y.
  • Journal Title: Circulation J 74(9) Pages: 1815-1821
• [Journal Article] A notch ligand, delta-like 1 functions as an adhesion molecule for mast cells. (2010)
  • Author(s): Murata A, Okuyama K, Sakano S, Kajiki M, Hirata T, Yagita H, Zuniga-Pflucker JC, Miyake K, Akashi-Takamura S, Moriwaki S, Niida S, Yoshino M, Hayashi S-I.
  • Journal Title: J Immunol 185(7) Pages: 3905-3912
• [Journal Article] Hyaluronan deficiency in tumor stroma impair macrophage trafficking and tumor neovascularization. (2010)
  • Author(s): Kobayashi N, Miyoshi S, Mikami T, Koyama H, Takeoka M, Sano K, Amano J, Isogai Z, Niida S, Oguri K, Okayama M, McDonald JA, Kimata K, Taniguchi S, Itano N.
  • Journal Title: Cancer Res 70(18) Pages: 7073-7083
• [Journal Article] Regulation of MyD88 aggregation and MyD88-dependent signaling pathway by sequestome 1 and histone deacetylase 6. (2010)
  • Author(s): Into T, Inomata M, Niida S, Murakami Y, Shibata KI.
  • Journal Title: J Biol Chem 285(46) Pages: 35759-69
• [Journal Article] Rho-kinase limits FGF-2-stimukated VEGF release in osteoblasts. (2010)
  • Author(s): Natsume H, 他
  • Journal Title: Bone Volume: 46 Pages: 1493-97
  • Peer Reviewed
• [Journal Article] Is structural remodeling of fibrillated atria the consequence of tissue hypoxia? (2010)
  • Author(s): Ogi H, 他
  • Journal Title: Circulation J Volume: 74 Pages: 1815-21
  • Peer Reviewed
• [Journal Article] A notch ligand, delta-like 1 functions as an adhesion molecule for mast cells. (2010)
  • Author(s): Murata A, 他
  • Journal Title: J Immunol Volume: 185 Pages: 3905-12
  • Peer Reviewed
• [Journal Article] Hyaluronan deficiency in tumor stroma impair macrophage trafficking and tumor neovascularization. (2010)
  • Author(s): Kobayashi N, 他
  • Journal Title: Cancer Res Volume: 70 Pages: 7073-83
  • Peer Reviewed
• [Journal Article] Regulation of MyD88 aggregation and MyD88-dependent signaling pathway by sequestome 1 and histone deacetylase 6. (2010)
  • Author(s): Into T, 他
  • Journal Title: J Biol Chem, 他 Volume: 285 Pages: 35759-69
  • Peer Reviewed
• [Journal Article] 発生期の血管新生に関与するペリサイトのリクルートメント (2010)
  • Author(s): 山本誠士, 他
  • Journal Title: 脈管学 Volume: 50 Pages: 197-201
  • Peer Reviewed
• [Journal Article] Bone mineral analysis through dual energy X-ray absortptiometry in laboratory animals. (2009)
  • Author(s): Tsujio M, Mizorogi T, Kitamura I, Maeda Y, Nishijima K, Kuwahara S, Ohno T, Niida S, Nagaya M, Saito R, Tanaka S.
  • Journal Title: J Veterinary Med Sci 71 Pages: 1493-1497
• [Journal Article] Bone mineral analysis through dual energy X-ray absorptiometry in laboratory animals. (2009)
  • Author(s): Tsujio M., 他
  • Journal Title: J Veterinary Med Sci 71 Pages: 1493-1497
  • Peer Reviewed
• [Journal Article] γ-グルタミルトランスペプチダーゼの骨破壊作用 (2008)
  • Author(s): 新飯田俊平
  • Journal Title: 福岡医学 99 Pages: 209-213
  • NAID: 120001036663
  • Peer Reviewed
• [Journal Article] γ-GTPを標的とした関節破壊抑制 (2008)
  • Author(s): 新飯田俊平
  • Journal Title: 細胞 40 Pages: 386-389
• [Presentation] マウス脳血管内皮細胞株を用いたEndothelial microparticles(EMP)のin vitro産生系の確立および疾患バイオマーカーとしての可能性の検討 (2010)
  • Author(s): 山本誠士, 他
  • Organizer: 第33回日本分子生物医学会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] Aging impacts on miRNAs expression in blood. (2010)
  • Author(s): 村松昌, 他
  • Organizer: 第2回日本RNAi研究会
  • Place of Presentation: 広島
  • Year and Date: 2010-08-28
• [Presentation] 骨吸収マーカーを用いた骨粗鬆症一次スクリーニングの検診成績 (2010)
  • Author(s): 森脇佐和子, 他
  • Organizer: 第28回日本骨代謝学会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-23
• [Presentation] CNS pericytes originate from the circulating hematopoietic progenitors. (2010)
  • Author(s): Yamamoto S, 他
  • Organizer: 16th World Congress of Basic and Clinical Pharmacology
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2010-07-20
• [Presentation] NG2 positive cerebral microvascular pericytes are potentially derived from circulating myeloid progenitors. (2010)
  • Author(s): Yamamoto S, 他
  • Organizer: 16th International Vascular Biology Meeting
  • Place of Presentation: 米国・加州
  • Year and Date: 2010-06-20
• [Presentation] Proteomic analysis of the Notch3-expressing cells and the microvessels of CADASIL brain. (2010)
  • Author(s): Watanabe A, 他
  • Organizer: International conference on Alzheimer's disease
  • Place of Presentation: 米国・ホノルル
  • Year and Date: 2010-06-15
• [Presentation] Rho-kinase阻害剤は骨芽細胞においてトランスフォーミング増殖因子-β(TGF-β)による血管内皮細胞増殖因子(VEGF)産生を抑制する. (2010)
  • Author(s): 徳田治彦, 小澤修, 原田敦, 細井孝之, 新飯田俊平
  • Organizer: 第52回日本老年医学会
• [Presentation] 骨吸収マーカーを用いた骨粗鬆症一次スクリーニングの検診成績. (2010)
  • Author(s): 森脇佐和子, 上西一弘, 徳田治彦, 原田敦, 濃沼信夫, 新飯田俊平
  • Organizer: 第28回日本骨代謝学会
• [Presentation] Aging impacts on miRNAs expression in blood. (2010)
  • Author(s): 村松昌, 山本誠士, 森脇佐和子, 本山昇, 徳田治彦, 新飯田俊平
  • Organizer: 日本RNAi研究会
• [Presentation] 骨粗鬆症スクリーニングにおける尿中・-GTP の有用性についての検討. (2010)
  • Author(s): 田中伸哉, 森脇佐和子, 上西一弘, 濃沼信夫, 田中清, 池田義孝, 新飯田俊平
  • Organizer: 第16回埼玉骨粗鬆症研究会
• [Presentation] 脳微小血管網を構成するペリサイトは造血系細胞由来である. (2010)
  • Author(s): 山本誠士, 村松昌, Bon-nyeo Koo, 向山洋介, 喜多紗斗美, 岩本隆宏, 東英梨月, 堂本光子, 渡邊泰秀, 小室一成, 大澤毅, 高橋宏行, 高野健一, 生谷尚士, 長井良憲, 高津聖志, 薄井勲, 戸邉一之, 新飯田俊平, 澁谷正史, 松田直之, 服部裕一
  • Organizer: 第32回日本分子生物学会年会
• [Presentation] 脳微小血管網を構成するペリサイトは造血系細胞由来である. (2009)
  • Author(s): 山本誠士, 他
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-12
• [Presentation] Macrophage形成不全マウスおよびtime lapse imagingを用いたペリサイト前駆細胞の発生学的検討. (2009)
  • Author(s): 山本誠士, 他
  • Organizer: 第17回日本血管生物医学会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-09
• [Presentation] DNA損傷応答因子Chk2欠損による早期老化症モデルマウスの寿命延長 (2009)
  • Author(s): 松本恵, 他
  • Organizer: 第32回日本基礎老化学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-06-20
• [Presentation] 細菌由来GGTは新規の歯周炎病態因子か (2008)
  • Author(s): 森脇佐和子, 他
  • Organizer: 第50回歯科基礎医学会
  • Place of Presentation: 東京
  • Year and Date: 2008-09-23
• [Presentation] 歯肉溝滲出液中γ-グルタミルトランスペプチダーゼ値を用いた歯周診断システムの構築の可能性について (2008)
  • Author(s): 川添祐亮, 他
  • Organizer: 第1回日本口腔検査学会
  • Place of Presentation: 東京
  • Year and Date: 2008-08-23
• [Presentation] Toll-like receptor 2アゴニストによるRANKLおよびTNFa非依存的な破骨細胞誘導 (2008)
  • Author(s): 鈴木恵子, 他
  • Organizer: 第26回日本骨代謝学会
  • Place of Presentation: 大阪
  • Year and Date: 2008-07-19
• [Presentation] Toll-like receptor 2アゴニストによるRANKL-およびTNFa-非依存的な破骨細胞誘導 (2008)
  • Author(s): 鈴木恵子, 新飯田俊平, 山田庄司
  • Organizer: 第26回日本骨代謝学会
• [Presentation] 歯肉溝滲出液中γ-グルタミルトランスペプチダーゼ値を用いた歯周診断システムの構築の可能性について (2008)
  • Author(s): 川添祐亮, 宮内睦美, 田妻進, 古庄寿子, 鈴木恵子, 新飯田俊平, 高田隆
  • Organizer: 第1回日本口腔検査学会
• [Remarks] 特になし
• [Remarks]
  • URL: http://www.nils.go.jp/
• [Remarks]
  • URL: http://www.nils.go.jp/