Development of novel diagnostic technology for marfan syndrome using periodontal tissue

• Project/Area Number: 16K15844
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Periodontology
• Research Institution: Tohoku University
• Principal Investigator: Saito Masahiro 東北大学, 歯学研究科, 教授 (40215562)
• Co-Investigator(Kenkyū-buntansha): 吉田 恭子 (今中恭子) 三重大学, 医学系研究科, 准教授 (00242967) ; 石河 真幸 東北大学, 大学病院, 助教 (60432936)
• Co-Investigator(Renkei-kenkyūsha): 石河 真幸 東北大学, 歯学研究科, 助教 (60432936)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 結合組織疾患 / マルファン症候群 / 組織破壊 / 細胞外マトリックス / イメージング診断 / 解離性大動脈瘤 / 歯周炎 / モノクローナル抗体 / 弾性システム / 歯学 / トランスレーショナルリサーチ / 循環器 / バイオテクノロジー / 医療

Outline of Final Research Achievements

Marfan syndrome is a genetic connective tissue disease that caused by mutation of fibrillin-1 that is a major component of microfibril. Main cause of death of marfan syndrome is aortic aneurysm and dissection, however no reliable diagnostic method is available at present. In this project, we tried to develop a novel diagnostic technology of aortic aneurysm and dissection that investigating microfibril structure using anti-fibrillin-1 antibody. We generated immunostaining technology that is able to stain microfibril in the human aorta using anti-fibrillin-1 antibody. The diagnostic technology that suspect aortic aneurysm and dissection is going to develop by using gigival tissue obtained from marfan syndrome patient.

Research Products

• [Journal Article] Fibrillin-1 insufficiency alters periodontal wound healing failure in a mouse model of Marfan syndrome. (2018)
  • Author(s): Handa K, Abe S, Suresh VV, Fujieda Y, Ishikawa M, Orimoto A, Kobayashi Y, Yamada S, Yamaba S, Murakami S, Saito M.
  • Journal Title: Arch Oral Biol. Volume: 90 Pages: 53-60
  • DOI: 10.1016/j.archoralbio.2018.02.017
  • Peer Reviewed / Open Access
• [Journal Article] Metal ions from S‐PRG filler have the potential to prevent periodontal disease (2017)
  • Author(s): Yoko Iwamatsu‐Kobayashi, Syouta Abe, Yoshiyasu Fujieda, Ai Orimoto, Masafumi Kanehira, Keisuke Handa, Venkata Suresh Venkataiah, Wei Zou, Masaki Ishikawa, Masahiro Saito
  • Journal Title: Clinical and Experiment Dental Research Volume: 3 Issue: 4 Pages: 126-133
  • DOI: 10.1002/cre2.70
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] F-spondin negatively regulates dental follicle differentiation through the inhibition of TGF-beta activity. (2017)
  • Author(s): Orimoto A, Kurokawa M, Handa K, Ishikawa M, Nishida E, Aino M, Mitani A, Ogawa M, Tsuji T Saito M
  • Journal Title: Arch Oral Biol Volume: 79 Pages: 7-13
  • DOI: 10.1016/j.archoralbio.2017.02.019
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 歯周組織再生医療の開発と課題 (2017)
  • Author(s): 齋藤正寛
  • Organizer: 第16回日本再生医療学会総
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-07
• [Presentation] 腔と全身の疾患を繋げる共通の標的：メカノバイオロジーを介した結合組織疾患発症機構の解析 (2017)
  • Author(s): 齋藤正寛
  • Organizer: 第147回日本歯科保存学会秋季学術大会
  • Invited
• [Presentation] Role of ADAMTSL6 on aortic aneurysm and dissection in Marfan syndrome (2017)
  • Author(s): Masahiro Saito
  • Organizer: Gordon reserch conference Elastin, Elastic fibers & microfibrils
  • Int'l Joint Research
• [Presentation] 脂肪由来幹細胞を用いた歯周組織再生療法の開発:ブタモデルを用いた他家移植モデルの確立 (2017)
  • Author(s): V ベンカタ スレッシュ、半田 慶介、竹立 匡秀、村上 伸也、齋藤 正寛
  • Organizer: 第146回保存学会日本歯科保存学会春季学術大会
• [Presentation] ADAMTSL6βを介したMarfan症候群の解離性大動脈瘤発症機構の解析 (2017)
  • Author(s): 折本 愛、二木 正晴、石河 真幸、半田 慶介、齋藤 正寛
  • Organizer: 第146回保存学会日本歯科保存学会春季学術大会2017年6月9日
• [Presentation] Pannexin 3は新骨形成制御因子である (2017)
  • Author(s): 石河真幸、 Geneva L. Williams、折本愛 、半田慶介 、山田吉彦 、齋藤正寛
  • Organizer: 結合組織学会
• [Presentation] ADAMTS superfamilyによるMarfan症候群の解離性大動脈瘤発症機構の解析 (2017)
  • Author(s): 折本愛、石河 真幸、半田慶介、千々岩みゆき、望月早月、村澤祐介、磯貝善 蔵、岡田保典、齋藤正寛
  • Organizer: 結合組織学会
• [Presentation] ADAMTSL6beta exacerbates tissue destruction of aortic aneurysm and dissection in Marfan syndrome mouse model through promotion of ADAMTS4 activity. (2016)
  • Author(s): Orimoto A, Murasawa Y, Isogai Z, Chijiiwa M, Mochizuki S, Imanaka- Yoshida K, Okada Y and Saito M
  • Organizer: ASMB2016
  • Place of Presentation: St. Petersburg, Florida, USA
  • Year and Date: 2016-11-15
  • Int'l Joint Research / Invited
• [Presentation] 未分化骨芽細胞細胞移植による歯槽骨再生療法について（第一報）ブタ歯槽骨由来未分化骨芽細胞の特性 (2016)
  • Author(s): 半田慶介、丸山顕太郎、根本英二、齋藤正寛
  • Organizer: 第59回秋季日本歯周病学会学術大会
  • Place of Presentation: 新潟
  • Year and Date: 2016-10-07
• [Presentation] Immature osteoblast derived from micro-mini pig for periodontal tissue regeneration. (2016)
  • Author(s): V. Venkata Suresh, Keisuke Handa, Masahiro Saito.
  • Organizer: IADR
  • Place of Presentation: Seoul, South Korea
  • Year and Date: 2016-06-23
  • Int'l Joint Research
• [Presentation] ADAMTSL6β accelerated ADAMTS4 activity to enhance DAA in MFS. (2016)
  • Author(s): Ai Orimoto, Masaharu Futagi, Masaki Ishikawa, Keisuke Handa, Masahiro Saito
  • Organizer: IADR
  • Place of Presentation: Seoul, South Korea
  • Year and Date: 2016-06-22
  • Int'l Joint Research