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Development of TNF-receptor Antagonists which have both Anti-inflammatory Action and Bone Formation Activity and Apply Them for the Treatment of Periodontal Diseases.

Research Project

Project/Area Number 24390413
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Functional basic dentistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

OHYA Keiichi  東京医科歯科大学, 歯学部, 非常勤講師 (10126211)

Co-Investigator(Kenkyū-buntansha) AOKI Kazuhiro  東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (40272603)
TAKAHASHI Mariko  東京医科歯科大学, 歯学部, 技術職員 (90334440)
二藤 彰  鶴見大学, 歯学部, 教授 (00240747)
Co-Investigator(Renkei-kenkyūsha) NIFUJI Akira  鶴見大学, 歯学部, 教授 (00240747)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2014: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2012: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
KeywordsTNF拮抗薬 / 硬組織 / 破骨細胞 / 骨芽細胞 / 骨形成 / 骨吸収 / 歯周病 / 炎症性疾患 / 骨吸収阻害薬 / 骨形成促進 / 抗炎症 / DDS / ナノゲル / TNF / ペプチド薬 / BMP / ペプチドアンタゴニスト
Outline of Final Research Achievements

Inflammation caused by periodontal disease, which is a typical disease of the dental region, induces jaw bone resorption. Jaw bone resorption finally promotes the loss of teeth, leading to a decline of masticatory function. So to aim the development of drug therapies that can treat and prevent periodontal disease, we examined the cyclic peptide W9, which inhibits the binding of TNF and TNF receptor. W9 peptide showed a bone resorption inhibitory action through the mechanism that inhibits the interaction of RANK / RANKL, which is important for a growth and differentiation process of osteoclasts. In addition, W9 peptide was found to possess a bone formation promoting action as shown by the detailed study of the effect of the W9 peptides on bone. Further, by exploring the DDS system of W9 peptide, the peptide was shown to be useful for the treatment of the inflammatory bone resorption disease such as the periodontal disease.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (19 results)

All 2014 2013 2012 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (10 results) Remarks (1 results)

  • [Journal Article] A disulfide bond-replacement strategy enables the efficient design of artificial therapeutic peptides2014

    • Author(s)
      Kazuhiro Aoki, Miki Maeda, Takashi Nakae, Yohei Okada, Keiichi Ohya, Kazuhiro Chiba
    • Journal Title

      Tetrahedron

      Volume: 70 Issue: 42 Pages: 7774-7779

    • DOI

      10.1016/j.tet.2014.05.079

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Use of a gelatin hydrogel membrane containing β-tricalcium phosphate for guided bone regeneration enhances rapid bone formation2014

    • Author(s)
      Noritake, K. Kuroda, S. Nyan, M. Atsuzawa, Y. Uo, M. Ohya, K. Kasugai, S
    • Journal Title

      Dental Materials Journal

      Volume: 33 Issue: 5 Pages: 674-680

    • DOI

      10.4012/dmj.2014-123

    • NAID

      130004696774

    • ISSN
      0287-4547, 1881-1361
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gelatin hydrogel as a carrier of recombinant human fibroblast growth factor-2 during rat mandibular distraction.2014

    • Author(s)
      Kimura A, Kabasawa Y, Tabata Y, Aoki K, Ohya K, Omura K
    • Journal Title

      J Oral Maxillofac Surg.

      Volume: 72 Issue: 10 Pages: 2015-2031

    • DOI

      10.1016/j.joms.2014.03.014

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gelatin hydrogel carrier with the W9-peptide elicits synergistic effects on BMP-2-induced bone regeneration.2013

    • Author(s)
      Mamun, A.Khan, M. Alles, N. Matsui, M. Tabata, Y. Ohya, K. Aoki, K
    • Journal Title

      J Oral Biosciences

      Volume: 55 Pages: 217-223

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stimulation of bone formation in cortical bone of mice treated with a receptor activator of nuclear factor-κB ligand (RANKL)-binding peptide that possesses osteoclastogenesis inhibitory activity.2013

    • Author(s)
      Furuya Y, Inagaki A, Khan M, Mori K, Penninger JM, Nakamura M, Udagawa N, Aoki K, Ohya K, Uchida K, Yasuda H
    • Journal Title

      J Biol Chem

      Volume: 288 Issue: 8 Pages: 5562-5571

    • DOI

      10.1074/jbc.m112.426080

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The local administration of TNF-alpha and RANKL antagonist peptide promotes BMP-2-induced bone formation.2013

    • Author(s)
      Abdulla Al Masud Khan
    • Journal Title

      J Oral Biosciences

      Volume: 55 Pages: 47-54

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Peptide-based delivery to bone.2012

    • Author(s)
      Aoki K
    • Journal Title

      Advanced Drug Delivery Reviews

      Volume: 64 Issue: 12 Pages: 1220-1238

    • DOI

      10.1016/j.addr.2012.05.017

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Osteoclast formation and differentiation : An overview.2012

    • Author(s)
      Soysa N.S
    • Journal Title

      J Med Dent Sci

      Volume: 59 Pages: 65-74

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] RANKL結合ペプチドの骨吸収抑制作用と骨形成促進作用2014

    • Author(s)
      青木和広、菅森泰隆、加藤玄樹、上原智己、新井祐貴、Md.Zahirul Haq Bhuyan、Neil Alles、Masud Khan、高橋真理子、田村幸彦、若林則幸、大谷啓一
    • Organizer
      第56回歯科基礎医学会学術大会・総会
    • Place of Presentation
      福岡
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Ⅱ型ウシコラーゲン誘導のマウス関節リウマチモデルを用いたRANKL結合ペプチドの骨形成促進作用と骨吸収抑制作用2014

    • Author(s)
      加藤玄樹、清水康広、菅森泰隆、田村幸彦、小野卓史、大谷啓一、青木和広
    • Organizer
      第56回歯科基礎医学会学術大会・総会
    • Place of Presentation
      福岡
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] RANKL-binding peptides increased bone formation in a murine calvarial defect model2014

    • Author(s)
      Sugamori,Y. Honma,M. Kato,G. Tamura,Y. Furuya,Y. YasudaH, Tabata,Y. Udagawa,N. Ohya,K. Suzuki,H. Aoki,K
    • Organizer
      アメリカ骨代謝学会2014
    • Place of Presentation
      ヒューストン、アメリカ
    • Year and Date
      2014-09-12 – 2014-09-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] RANKL結合ペプチドはマウス頭蓋骨欠損モデルの骨新生を促進する2014

    • Author(s)
      菅森泰隆、本間雅、加藤玄樹、田村幸彦、古屋優里子、保田尚孝、田畑泰彦、宇田川信之、大谷啓一、鈴木洋史、青木和広
    • Organizer
      第32回日本骨代謝学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-07-24 – 2014-07-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] マウス骨吸収モデルにおいてPEG架橋したCHPナノゲルは合成ペプチドW9の骨量減少抑制効果を増強した2014

    • Author(s)
      佐藤俊三、青木和広、田村幸彦、大谷啓一
    • Organizer
      第34回日本歯科薬物療法学会学術大会
    • Place of Presentation
      大阪
    • Year and Date
      2014-06-21 – 2014-06-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] CHPナノゲル担体のPEG架橋により骨吸収抑制ペプチドの作用は増強する-低Ca食飼育によるマウス骨吸収促進モデルにおける検討.2013

    • Author(s)
      佐藤 俊三、田村 幸彦、大谷 啓一、青木 和広.
    • Organizer
      第33回日本歯科薬物療法学会学術大会
    • Place of Presentation
      東京/東京医科歯科大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] An Osteoprotegerin-like Peptide Inhibits Bone Loss in Collagen Type II-Induced Murine Arthritis.2013

    • Author(s)
      Kato, G. Maeda, M. Alles, N. Mamun, A. Khan, M. Sugamori, Y. Takahashi, M. Tamura, Y. Murali, R. Ohya, K. Aoki, K.
    • Organizer
      IBMS/JSBMR第2回合同国際会議
    • Place of Presentation
      神戸/神戸コンベンションセンター・神戸ポートピアホテル
    • Related Report
      2013 Annual Research Report
  • [Presentation] Bone resorption inhibitor peptides work as a bone formation stimulator.2013

    • Author(s)
      Aoki,K. Murali,R. Ohya,K.
    • Organizer
      The 3rd Tri-University Consortium on Oral Science and Education
    • Place of Presentation
      東京/東京医科歯科大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] An Osteoprotegerin-like Peptide Prevents Bone Loss in Collagen-Induced Murine Arthritis.2013

    • Author(s)
      Kato,G. Shimizu,Y. Mamun,M. Murali,R. Ohya,K. Aoki,K.
    • Organizer
      The 3rd Tri-University Consortium on Oral Science and Education
    • Place of Presentation
      東京/東京医科歯科大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] RANKL-Mediated Bone Formation By TNF-alpha Antagonist Peptide2012

    • Author(s)
      Khan M
    • Organizer
      IADR GENERAL SESSION
    • Place of Presentation
      Iguacu Falls, BRAZIL
    • Related Report
      2012 Annual Research Report
  • [Remarks] 硬組織薬理学分野

    • URL

      http://www.tmd.ac.jp/hpha/index.html

    • Related Report
      2014 Annual Research Report

URL: 

Published: 2012-04-24   Modified: 2019-07-29  

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