Gene network analyses of AD in periodontitis-affected gingival tissue

• Project/Area Number: 15K11382
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Periodontology
• Research Institution: Niigata University
• Principal Investigator: KUBOTA Takehiko 新潟大学, 医歯学総合病院, 講師 (50303136)
• Co-Investigator(Kenkyū-buntansha): 丸山 智 新潟大学, 医歯学総合病院, 講師 (30397161)
• Project Period (FY): 2015-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 医療・福祉 / 歯周病 / アルツハイマー病 / 遺伝子解析 / 免疫病理学 / ネットワーク解析 / 遺伝子 / 免疫病理 / 歯学 / 遺伝子発現 / 免疫学 / 病理学 / タンパク質局在

Outline of Final Research Achievements

We have first reported that the significantly elevated expression of Amyloid beta (A4) precursor protein (APP) and Neprilysin (NEP) transcript levels in human periodontitis-affected gingival tissues. The APP-expressing cells in inflamed gingival tissues were mainly macrophages, whereas NEP were expressed in neutrophils and fibroblasts (Archs Oral Biol 2017). The series of our research on inflammatory tissue metabolisms in periodontitis-affected gingival tissues including MMP/TIMP balance and Alzheimer’s disease(AD)-related gene networks won the 2018 senior investigator award from Japanese Society of Periodontology. The review paper was published in Journal of JSP 2018.

Academic Significance and Societal Importance of the Research Achievements

歯周病と認知症の主体であるアルツハイマー病（AD）の関係は、加齢・炎症に伴う歯周－全身関連疾患として注目を集めている。我々は、歯周炎歯肉組織で、AD原因遺伝子のひとつであるAmyloid beta precursor protein　(APP)をはじめAD関連遺伝子群が発現亢進していることを発見し、一連の研究を行ってきた。その結果、歯周病とADに共通する生物学的ネットワークから、慢性歯周炎が炎症を介してアルツハイマー病のリスクとなりうる機序の一端を明らかにした。歯周炎の予防・治療が認知症を防ぐとなれば、社会的意義が高く、超高齢化社会に向け極めて重要な研究成果を発信したこととなる。

Research Products

• [Journal Article] 歯周炎歯肉組織局所の細胞外マトリックス代謝調節遺伝子発現解析と全身疾患の関連解明 (2018)
  • Author(s): 久保田 健彦
  • Journal Title: 日本歯周病学会雑誌 Volume: 60 Pages: 123-130
  • Peer Reviewed / Open Access
• [Journal Article] Expression of neprilysin in periodontitis-affected gingival tissues. (2017)
  • Author(s): Nezu A, Kubota T, Maruyama S, Nagata M, Nohno K, Morizumi T, Yoshie H.
  • Journal Title: Arch Oral Biol. Volume: 79 Pages: 35-41
  • DOI: 10.1016/j.archoralbio.2017.03.003
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Expression od neprilysin in periodontitis-affected gingival tissues (2017)
  • Author(s): Nezu A, Kubota T, Maruyama S, Nagata M, Horimizu M, Nohno K, Hokari T, Morozumi T, Yoshie H
  • Journal Title: J Int Academy Periodontol Volume: 19
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 歯周炎歯肉組織局所の細胞外マトリックス代謝調節遺伝子発現解析と全身疾患の関連解明 (2018)
  • Author(s): 久保田 健彦
  • Organizer: 日本歯周病学会春季学術大会(第61回）
  • Invited
• [Presentation] 専門医が明かす歯周病 (2017)
  • Author(s): 久保田健彦
  • Organizer: まちなかキャンパス長岡・講座 医療見聞録II
  • Invited
• [Presentation] 専門医が明かす歯周病 (2017)
  • Author(s): 久保田健彦
  • Organizer: 2017年中国ハルビン歯科新発展研究会
  • Int'l Joint Research / Invited
• [Presentation] Expression of neprilysin in periodontitis-affected gingival tissues (2017)
  • Author(s): Nezu A, Kubota T, Maruyama S, Nagata M, Horimizu M, Nohno K, Hokari T, Morozumi T, Yoshie H
  • Organizer: 6th International Congress of Periodontology of the International Academy of Periodontology
  • Int'l Joint Research
• [Presentation] 歯と健康 ―専門医が明かす歯周病― (2017)
  • Author(s): 久保田健彦
  • Organizer: 2017年度 新潟妙高会 講演会
  • Invited
• [Presentation] 歯周炎罹患歯肉組織におけるネプリライシンの遺伝子発現レベルと免疫組織局在の解析 (2016)
  • Author(s): 根津 新, 久保田健彦, 丸山 智, 永田昌毅, 堀水 慎, 濃野 要, 保苅崇大, 両角俊哉, 朔 敬, 吉江弘正
  • Organizer: 平成28年度新潟歯学会第2回例会
  • Place of Presentation: 新潟大学歯学部 （新潟県新潟市）
  • Year and Date: 2016-11-05
• [Presentation] Expression of neprilysin in periodontitis-affected gingival tissue (2016)
  • Author(s): Nezu A, Kubota T, Maruyama S, Nagata M, Horimizu M, Nohno K, Hokari T, Morozumi T, Saku T, Yoshie H
  • Organizer: 102th Annual Meeting of the American Academy of Periodontology
  • Place of Presentation: San Diego Convention Center, San Diego, CA (USA)
  • Year and Date: 2016-10-10
  • Int'l Joint Research
• [Presentation] Expression of neprilysin in periodontitis-affected gingival tissues (2016)
  • Author(s): A Nezu, T Kubota, S Maruyama, M Nagata, M Horimizu, K Nouno, T Hokari, T Morozumi, T Saku, H Yoshie
  • Organizer: The 102nd Annual Meeting of the American Academy of Periodontology in collaboration with the Japanese Society of Periodontology and Japanese Academy of Clinical Periodontology
  • Place of Presentation: SanDiego, CA, USA
  • Year and Date: 2016-09-10
• [Presentation] 歯周病・歯周治療に対する疑問に答えるー明日から役立つー 歯周基本治療・歯周再生治療・インプラント・全身疾患 (2016)
  • Author(s): 久保田健彦
  • Organizer: 2016 群馬県藤岡市歯科医師会学術講演会
  • Place of Presentation: 藤岡商工会議所 (群馬県藤岡市）
  • Year and Date: 2016-01-30
  • Invited
• [Presentation] 歯周炎罹患歯肉組織におけるNeprilysin（Alzheimer病関連遺伝子）の発現 (2015)
  • Author(s): 根津新、久保田健彦、丸山智、永田昌毅、堀水慎、濃野要、保苅崇大、両角俊哉、朔敬、 吉江弘正
  • Organizer: 第58回秋季日本歯周病学会学術大会
  • Place of Presentation: アクトシティ浜松 (静岡県浜松市）
  • Year and Date: 2015-09-12
• [Presentation] Alzheimer’s diseases-related gene and protein expressions in periodontitis-affected gingival tissues (2015)
  • Author(s): Kubota T, Nezu A, Maruyama S, Horimizu M, Nohno K, Hokari T, Morozumi T, Saku T, Yoshie H
  • Organizer: Europerio 8
  • Place of Presentation: London (UK)
  • Year and Date: 2015-06-03
  • Int'l Joint Research