Guided control of keratinized epithelial mucosa as a next generation periodontal soft tissue regeneration

• Project/Area Number: 15H05026
• 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: Maekawa Kenji 岡山大学, 医歯薬学総合研究科, 准教授 (20304313)
• Co-Investigator(Kenkyū-buntansha): 大野 充昭 岡山大学, 医歯薬学総合研究科, 助教 (60613156) ; 渡辺 亮 京都大学, iPS細胞研究所, 特定拠点助教 (60506765) ; 秋山 謙太郎 岡山大学, 大学病院, 講師 (70423291) ; 窪木 拓男 岡山大学, 医歯薬学総合研究科, 教授 (00225195) ; 大島 正充 岡山大学, 医歯薬学総合研究科, 助教 (00548307)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2015: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
• Keywords: 角化歯肉 / 角化歯肉獲得法 / 基底膜 / Ⅳ型コラーゲン / 基底膜構成分子 / 付着歯肉 / 上皮角化 / 口腔粘膜 / 角化 / 上皮

Outline of Final Research Achievements

Keratinized gingiva around the tooth and dental implant is critical to maintain a healthy condition of periodontal and peri-implant tissues, however the mechanisms regulating keratinization of gingiva still remain unclear. In this study, we hypothesized that the basement membrane is a critical regulator of keratinization of the oral mucosal epithelium. From our results, we found out that the difference in keratinization of oral mucosa is associated with the composition of the basement membrane. In addition to this, the composition which highly expresses in keratinized gingiva induced human gingival epithelial cells to express keratinized marker in vitro.

Academic Significance and Societal Importance of the Research Achievements

本研究において，基底膜は口腔粘膜の角化を制御する重要な因子である可能性が示唆された。つまり，角化歯肉を誘導する基底膜を人工的に作製することで、自己組織移植を回避できる可能性，さらには角化に重要な基底膜分子の発現を亢進させる薬剤を非外科的に応用することで，生物学的に非角化歯肉部位を角化歯肉に誘導できる可能性を見出すことができた。

Research Products

• [Journal Article] Type IV collagen α6 chain is a regulator of keratin 10 in keratinization of oral mucosal epithelium. (2018)
  • Author(s): Komori T, Ono M, Hara ES, Ueda J, Nguyen HTT, Nguyen HT, Yonezawa T, Maeba T, Ono A, Takarada T, Momota R, Maekawa K, Kuboki T, Oohashi T
  • Journal Title: Sci Rep. Volume: 8 Pages: 2612-2612
  • DOI: 10.1038/s41598-018-21000-0
  • Peer Reviewed / Open Access
• [Presentation] 基底膜構成分子Type IV collagen α6は口腔粘膜上皮の角化を制御する (2018)
  • Author(s): 小盛大志，大野充昭，植田淳二，Nguyen Thi Thu Ha，前川賢治，大橋俊孝，窪木拓男
  • Organizer: 日本補綴歯科学会第127回学術大会
• [Presentation] Regulation of gingival keratinization by laminin332 (2017)
  • Author(s): Junji UEDA, Taishi KOMORI, Mitsuaki ONO, Emilio S HARA, Yuya YOSHIOKA, Wataru SONOYAMA, Kenji MAEKAWA, Takuo KUBOKI
  • Organizer: 95th General Session & Exhibition of the IADR
  • Place of Presentation: SanFrancisco, CA, USA
  • Year and Date: 2017-03-23
• [Presentation] 口腔粘膜上皮の角化制御におけるCollagen IV a6の役割 (2017)
  • Author(s): 小盛大志，大野充昭，植田淳二，Nguyen TTH，前川賢治，窪木拓男
  • Organizer: 第47回日本口腔インプラント学会
• [Presentation] 口腔粘膜上皮における角化因子の探索 (2016)
  • Author(s): 植田淳二，大野充昭，小盛大志，吉岡裕也，園山 亘，前川賢治，窪木拓男．
  • Organizer: 公益社団法人日本補綴歯科学会第125回学術大会
  • Place of Presentation: 金沢，日本
  • Year and Date: 2016-07-09
• [Patent(Industrial Property Rights)] 角化歯肉誘導剤 (2016)
  • Inventor(s): 窪木拓男，大野充昭，前川賢治，植田淳二，小盛大志.
  • Industrial Property Rights Holder: 国立大学法人 岡山大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-113309
  • Filing Date: 2016-06-07