Understanding of periodontal disease and peri-implantitis with stem cell disfunction

• Project/Area Number: 17H04392
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Prosthodontics/ Dental materials science and
• Research Institution: Okayama University
• Principal Investigator: AKIYAMA Kentaro 岡山大学, 大学病院, 講師 (70423291)
• Co-Investigator(Kenkyū-buntansha): 窪木 拓男 岡山大学, 医歯薬学総合研究科, 教授 (00225195) ; 大島 正充 徳島大学, 大学院医歯薬学研究部(歯学域), 准教授 (00548307) ; 大野 充昭 岡山大学, 医歯薬学総合研究科, 准教授 (60613156)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2017: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: 再生医療 / 間葉系幹細胞 / 加齢 / 加齢による機能変化 / 炎症性疾患 / 再生医学 / 宿主老化 / 間葉系幹細胞機能 / 老化関連疾患

Outline of Final Research Achievements

In this study, we investigated how the bone marrow-derived mesenchymal stem cells (MSCs) function is affected by host aging. And then, how the suppressed MSCs function contributes to the development of inflammatory diseases in periodontal tissues such as periodontal disease and peri-implantitis. As a result, in the experimentally induced periodontal disease model mice, increased bone resorption was observed in aged mice. Moreover, the function of MSCs derived from 50-week-old mice showed lower cell proliferation and osteoblast differentiation ability with higher adipocyte differentiation ability. More interestingly, MSCs from aged mice showed decreased immunoregulatory capacity.

Academic Significance and Societal Importance of the Research Achievements

本申請研究の成果は，宿主の加齢によりMSCs機能の低下，特に，骨芽細胞分化能と免疫調整機能の低下は，炎症性疾患に対する，抵抗力ならびに組織再生力の低下を意味し，病態の形成，進行に大きく影響することを明らかにした．MSCs機能低下をもたらす詳細なメカニズムはさらなる検討が必要ではあるものの，MSCs機能の低下を阻止することで疾患の重症化に歯止めをかける新規治療法開発につながる．

Research Products

• [Int'l Joint Research] ストラスブール 大学(フランス)
• [Presentation] OLDER PERIODONTITIS MODEL MICE SHOWED SEVERER BONE DEFECTS AND SPARSER MESENCHYMAL STEM CELLS DISTRIBUTION WITH MORE DIFFUSE PAN T CELLS INFILTRATION (2019)
  • Author(s): Kyaw Thu Aung, Kentaro Akiyama, Kenji Maekawa, Takuo Kuboki
  • Organizer: ISSCR
• [Presentation] HOST BONE-MARROW-DERIVED MESENCHYMAL STEM CELLS AND INFLAMMATORY CYTOKINES IN LONG BONE INJURERD MODEL (2019)
  • Author(s): AKIYAMA K, KOMI K, KUBOKI T
  • Organizer: ISSCR
• [Presentation] Comparison of bone defects and mesenchymal stem cells population in ligature induced young and old aged periodontitis mice models (2018)
  • Author(s): Kyaw Thu Aung, Kentaro Akiyama, Kenji Maekawa, Takuo Kuboki.
  • Organizer: JADR
  • Int'l Joint Research
• [Presentation] Older periodontitis model mice showed severer bone defects and sparse mesenchymal stem cells distribution in the periodontal defects. (2017)
  • Author(s): Kyaw thu Aung，Kentaro Akiyama, Kenji Maekawa, Takuo Kuboki
  • Organizer: JADR
  • Int'l Joint Research