Differentially expressed genes analysis by RNA-seq : Inflamed periodontal tissue of ligature-induced periodontitis in mice

• Project/Area Number: 17K17348
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Periodontology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: MAEKAWA Shogo 東京医科歯科大学, 歯学部附属病院, 特任助教 (20793574)
• Research Collaborator: KATAGIRI sayaka ; ONIZUKA satoru ; SASAKI naoki ; WATANABE kazuki ; OHTSU anri ; KOMAZAKI rina ; OGURA kohei ; AKIYAMA tohru ; IWATA takanori ; NITTA hiroshi ; IZUMI yuichi
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 結紮誘導歯周炎 / RNA sequencing / DAMPs / 発現変動遺伝子 / RNA-seq / 歯周病 / 急速な歯周組織破壊 / 歯周病学

Outline of Final Research Achievements

A silk ligature around second molar induced severe bone loss at 8 days after ligation. In vivo MicroCT analysis revealed that bone loss was initiated 3 to 5 days post ligation. RNA-seq analysis detected 12,852 genes (FPKM > 1.0 in at least one sample) that were categorized into 10 patterns by a hierarchical clustering approach. GO term enrichment analysis revealed that neutrophil chemotaxis and inflammatory responses expression profiles were significantly high in ligated gingiva. Interestingly, S100a8 mRNA expression level was significantly elevated in ligated gingiva. Histological analysis showed an increased number of TRAP-positive multinucleated cells at the ligated sites and higher S100A8 expressions in attached gingiva with ligation.
GO term enrichment analysis suggests that innate immune response related burst destruction of periodontal tissue in ligature-induced periodontitis mice model. Therefore, S100A8 may act as important role for rapid periodontal destruction.

Academic Significance and Societal Importance of the Research Achievements

本研究の結果より、急速な歯周組織破壊において、傷害関連分子パターンであるS100A8の関与が認められた。かねてより歯周組織の破壊は不定期かつ不規則に進行する(Random Burst Theory)とされていたが、本研究の結果より急速に進行する歯周炎のメカニズムの一端が解明された。今後、侵襲性歯周炎のような急速な歯周組織の破壊を伴う若い患者に対する、新たな治療のターゲットとなる可能性が示唆された。

Research Products

• [Presentation] Differentially expressed genes analysis by RNA-seq : Inflamed periodontal tissue of ligature-induced periodontitis in mice (2017)
  • Author(s): Shogo Maekawa, Satoru Onizuka, Sayaka Katagiri, Kohei Ogura, Anri Ohtsu, Rina Komazaki, Sayuri Udagawa, Naoki Sasaki, Kazuki Watanabe, Yasuo Takeuchi, Tohru Miyoshi-Akiyama, Hiroshi Nitta, Takanori Iwata, Yuichi Izumi
  • Organizer: 103rd Annual meeting of American Academy of Periodontology
  • Int'l Joint Research