Diagnostic and regenerative strategies for periodontal tissue based on the Positional HOX signature

• Project/Area Number: 20K09944
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57030:Conservative dentistry-related
• Research Institution: Health Sciences University of Hokkaido
• Principal Investigator: NAGASAWA Toshiyuki 北海道医療大学, 歯学部, 教授 (90262203)
• Co-Investigator(Kenkyū-buntansha): 岩崎 剣吾 大阪歯科大学, 歯学部, 准教授 (40401351)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: HOX / DLX5 / DLX6 / Barx1 / periodontal ligament / gingival fibroblasts / ALP / OPG / IL-6 / Periodontal ligament / Gingival fibroblast / dermal fibroblast / miRNA / 幹細胞 / 歯周炎 / 組織再生

Outline of Research at the Start

本研究では正常な歯周組織ならびに歯周炎でmiRNAおよびHOX遺伝子が分化・増殖を制御する機構について詳細に検討し、歯周炎における病的なHOX発現を診断するシステムを確立する。さらに正常なHOX遺伝子を発現した間葉系幹細胞を歯周組織欠損に移植することで、発生における組織再生を模した歯周組織再生療法の基盤を確立する。

Outline of Final Research Achievements

Purpose of this study was to examine HOX gene expression by fibroblasts in the periodontitis region. Microarray analysis was performed on gingival, periodontal ligament, lip and skin fibroblast cell lines to examine HOX gene expression. Periodontal ligament fibroblasts and gingival fibroblasts were isolated from the same patient at the time of orthodontic convenience removal, and gene expression was compared. DLX6 and Barx1 were high in periodontal ligament and gingival fibroblasts compared with lip and dermal fibroblasts. In particular, high expression of DLX5 was suggested to be characteristic of periodontal ligament fibroblasts.

Academic Significance and Societal Importance of the Research Achievements

生体内に分布する間葉系幹細胞は異なるHOX遺伝子を発現し、細胞分化と組織の形成を制御することが報告されている。また関節リウマチの病変部では特徴的なHOX遺伝子の発現が認められることも報告され、HOX遺伝子は正常な組織の発生を制御するだけでなく、発現パターンによっては組織破壊への方向に導くことも示唆されている。これらの背景から歯周組織に特徴的なHOX遺伝子を明らかにすることで解剖学的に異なる部位における疾患の類似性および差異が明らかとなり、分子基盤に基づく治療が導入できる可能性が期待される。特に歯周組織再生においては幹細胞から歯根膜、歯槽骨および歯肉への分化を制御する基盤となることが期待される。

Research Products

• [Journal Article] Increase in Bifidobacterium is a characteristic of the difference in the salivary microbiota of pregnant and non-pregnant women. (2022)
  • Author(s): Kato S, Nagasawa T, Uehara O, Shimizu S, Sugiyama N, Hasegawa-Nakamura K, Noguchi K, Hatae M, Kakinoki H, Furuichi Y.
  • Journal Title: BMC Oral Health. Volume: 22 Issue: 1 Pages: 260-260
  • DOI: 10.1186/s12903-022-02293-0
  • Peer Reviewed / Open Access
• [Journal Article] Gut fora alterations due to lipopolysaccharide derived from Porphyromonas gingivalis (2022)
  • Author(s): Sugiyama N, Uehara O, Morikawa T, Paudel D, Ebata K, Hiraki D, Harada F, Yoshida K, Kato S, Nagasawa T, Miura H, Abiko Y, Furuichi Y.
  • Journal Title: Odontology Volume: Mar 25 Issue: 4 Pages: 673-681
  • DOI: 10.1007/s10266-022-00703-x
  • Peer Reviewed / Open Access
• [Journal Article] The effect of Porphyromonas gingivalis on the gut microbiome of mice in relation to aging (2022)
  • Author(s): 58.Sarita Giri, Osamu Uehara, Ayuko Takada, Durga Paudel, Tetsuro Morikawa, Toshiya Arakawa, Toshiyuki Nagasawa, Yoshihiro Abiko, Yasushi Furuichi
  • Journal Title: J Periodont Res Volume: 57 Issue: 6 Pages: 1256-1266
  • DOI: 10.1111/jre.13062
  • Peer Reviewed / Open Access
• [Journal Article] Metformin accelerates wound healing by Akt phosphorylation of gingival fibroblasts in insulin-resistant prediabetes mice (2022)
  • Author(s): 54.Hiromi Kominato, Kohei Takeda, Koji Mizutani, Risako Mikami, Daisuke Kido, Prima Buranasin, Natsumi Saito , Shu Takemura , Keita Nakagawa , Toshiyuki Nagasawa , Takanori Iwata
  • Journal Title: J Periodontol Volume: 93 Issue: 2 Pages: 256-158
  • DOI: 10.1002/jper.21-0362
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Draft Genome Sequence of Neisseria mucosa Strain HSUH001, Isolated from Aggressive-Periodontitis Lesion (2021)
  • Author(s): 53.Masatoshi Yamashita, Toshiyuki Nagasawa, Satsuki Kato, Hiroshi Miyakawa, Mari Fujita, Yasushi Furuichi, and Keiji Nagano
  • Journal Title: Microbiol Resour Announc. Volume: 13 Issue: 19 Pages: 00238-21
  • DOI: 10.1128/mra.00238-21
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of the virulence of Aggregatibacter actinomycetemcomitans through the analysis of leukotoxin. (2021)
  • Author(s): Toshiyuki Nagasawa, Satsuki Kato, Yasushi Furuichi
  • Journal Title: Methods Mol Biol. Volume: 2210 Pages: 185-193
  • DOI: 10.1007/978-1-0716-0939-2_18
  • ISBN: 9781071609385, 9781071609392
  • Peer Reviewed
• [Journal Article] The Periodontopathic Bacteria in Placenta, Saliva and Subgingival Plaque of Threatened Preterm Labor and Preterm Low Birth Weight Cases: A Longitudinal Study in Japanese Pregnant Women (2020)
  • Author(s): Changchang Ye 1 , Sayaka Katagiri 2 , Naoyuki Miyasaka 3 , Hiroaki Kobayashi 4 , Thatawee Khemwong 2 , Toshiyuki Nagasawa 5 , Yuichi Izumi 2
  • Journal Title: Clin Oral Investig Volume: 24 Issue: 12 Pages: 4261-4270
  • DOI: 10.1007/s00784-020-03287-4
  • Peer Reviewed / Open Access / Int'l Joint Research