the unravelling of the role of cathepsin in gingival overgrowth

• Project/Area Number: 15K11393
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Periodontology
• Research Institution: Kyushu University
• Principal Investigator: Yamashita Akiko 九州大学, 歯学研究院, 助教 (70511319)
• Co-Investigator(Kenkyū-buntansha): 中西 博 九州大学, 歯学研究院, 教授 (20155774) ; 西村 英紀 九州大学, 歯学研究院, 教授 (80208222) ; 岩下 未咲 九州大学, 大学病院, 助教 (80611326)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 歯肉増殖症 / カテプシン / 歯肉増殖

Outline of Final Research Achievements

We previously suggested complete loss of Cathepsin-L function promoted gingival overgrowth.SPOCK-1,belonging to proteoglycan family, is a specific inhibitor of CtsL. The aim of this study is to investigate the role of SPOCK-1 in DIGO.
Human gingival fibroblasts were collected from patients who underwent flap operations.The cells were stimulated with Phenytoin (PHE), Cyclosporin A (CsA) or Nifedipine (NFE). The mRNA and protein levels of SPOCK-1 were examined by quantitative real time PCR and western blotting. As in vivo study, Spock-1 transgenic mice and wild-type littermates were generated, grown, and sacrificed. Gingival appearance was observed by microscopy. The results indicated that PHE, CsA and NFD promoted the expression of SPOCK-1 both at mRNA and protein level. The gingiva of Spock-1 transgenic mice exhibited different degree of fibrosis.SPOCK-1 upregulation was common among the three drug used, which may indicate the importance of SPOCK-1 in the pathophysiology of DIGO.

Research Products

• [Presentation] 薬剤性歯肉増殖症におけるspock-1の役割 (2017)
  • Author(s): Rehab Alshargabi, 高野愛子, 山下明子，豊田啓介, 岩下未咲，佐野朋美，竹下正章，鶴田満大，松永紘明，眞田大樹, 相田宜利，讃井彰一，西村英紀
  • Organizer: 平成29年度日本歯周病学会60周年記念京都大会
• [Presentation] Epicatechin down-regulates inflammatory genes in adipocytes co-cultured with endotoxin-activated macrophages. (2017)
  • Author(s): Akiko Yamashita, Tomomi Sano, Shintaro Nagayasu, Misaki Iwashita, Takanori Shinjo, Fusanori Nishimura
  • Organizer: 95th IADR General Session
  • Int'l Joint Research
• [Presentation] The effect of cathepsin-B deficiency on gingival overgrowth in mice. (2016)
  • Author(s): Akiko Yamashita, Alshargabi Rehab Yahya Fara Sallam, Takanori Shinjyo, Misaki Iwashita, Hiroaki Matsunaga, Mitsudai Tsuruta, Yoko Hashimoto, Fusanori Nishimura
  • Organizer: 94th IADR General Session
  • Place of Presentation: Ｓｅｏｕｌ，Ｒｅｐｕｂｌｉｃ ｏｆ Ｋｏｒｅａ
  • Year and Date: 2016-06-22
  • Int'l Joint Research
• [Presentation] The effect of cathepsin-B deficiency on gingival overgrowth in mice. (2016)
  • Author(s): Alshargabi Rehab Yahya Fara Sallam, Akiko Yamashita, Takanori Shinjyo, Misaki Iwashita, Hiroaki Matsunaga, Mitsudai Tsuruta, Yoko Hashimoto, Fusanori Nishimura
  • Organizer: 第59回春季日本歯周病学会学術大会
  • Place of Presentation: 鹿児島市
  • Year and Date: 2016-05-21
• [Presentation] The effect of cathepsin-B deficiency on gingival overgrowth in mice. (2016)
  • Author(s): Alshargabi Rehab Yahya Fara Sallam
  • Organizer: 2016 spring meeting of the Japanese Society of Periodontology
  • Place of Presentation: 鹿児島
  • Year and Date: 2016-05-20