The mechanisms of occlusal trauma focusing on mechanosensing by osteocyte

• Project/Area Number: 20K23020
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0907:Oral science and related fields
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Tsuchiya Yosuke 東京医科歯科大学, 歯学部附属病院, 医員 (40882072)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 咬合性外傷 / 骨細胞 / 歯根膜細胞 / メカニカルストレス

Outline of Research at the Start

咬合性外傷は歯周炎を増悪させる主要な修飾因子であるが、外傷性咬合が骨破壊を増悪させるメカニズムについては不明な点が多い。
本研究では、歯周炎、咬合性外傷モデルマウスを用いて細菌、メカニカルストレスの存在と骨吸収の関連を明らかにする。また、歯周組織からサンプルを採取し、遺伝子発現変化をRNAシークエンス (RNAseq) にて網羅的に解析する。In vitroにおいてメカニカルストレスに対する応答を担う骨細胞、歯根膜細胞に着目しメカニカルストレス存在下における動態を評価するとともに、RNAseqより著明な発現変化を認めた遺伝子の機能解析を行うことによりメカニズムの検討を行う。

Outline of Final Research Achievements

Mice were divided into the following four groups: periodontitis (Pe) group, occlusal trauma+periodontitis(Pe+OT) group, occlusal trauma (OT) group and a control (Co) group.Pe+OT group showed significantly more bone loss than that of the Pe group at 8days after treatment.In addition, OT group showed more bone loss than that of Co group at 8days after treatment. These data suggesting that occlusal trauma is an aggravating factor for periodontitis and that occlusal trauma contributes to bone resorption in the mouse experiment.In addition, gingiva and alveolar bone samples were collected from the above four groups 3 days after each treatment, and comprehensive analysis using RNA-seq revealed that many genes with altered expression were found in the Pe+OT groups compared to the Pe group.

Academic Significance and Societal Importance of the Research Achievements

咬合性外傷はかねてから歯周病の増悪に寄与する共同破壊因子として示されているものの、動物実験や臨床における症例観察研究、介入研究による根拠がほとんどでありその作用機序を分子生物学的に検討しようとした研究は乏しい。咬合性外傷がどの様なメカニズムで発生するか、その病因について解明することは臨床的な歯周病の治療戦略上有意義であり、歯周治療における咬合治療の必要性を裏付ける重要なエビデンスになりうる。今後さらなる解析を行いメカニズムの同定を目指す。

Research Products

• [Journal Article] Porphyromonas gingivalis Administration Induces Gestational Obesity, Alters Gene Expression in the Liver and Brown Adipose Tissue in Pregnant Mice, and Causes Underweight in Fetuses (2022)
  • Author(s): Yoshida S、Hatasa M、Ohsugi Y、Tsuchiya Y、Liu A、Niimi H、Morita K、Shimohira T、Sasaki N、Maekawa S、Shiba T、Hirota T、Okano T、Hirose A、Ibi R、Noritake K、Tomiga Y、Nitta H、Suzuki T、Takahashi H、Miyasaka N、Iwata T、Katagiri S
  • Journal Title: Frontiers in Cellular and Infection Microbiology Volume: 11 Pages: 1-15
  • DOI: 10.3389/fcimb.2021.745117
  • Peer Reviewed / Open Access
• [Journal Article] Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease (2021)
  • Author(s): Lin Peiya、Niimi Hiromi、Ohsugi Yujin、Tsuchiya Yosuke、Shimohira Tsuyoshi、Komatsu Keiji、Liu Anhao、Shiba Takahiko、Aoki Akira、Iwata Takanori、Katagiri Sayaka
  • Journal Title: International Journal of Molecular Sciences Volume: 22 Issue: 16 Pages: 8900-8900
  • DOI: 10.3390/ijms22168900
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Low-Level Erbium-Doped Yttrium Aluminum Garnet Laser Irradiation Induced Alteration of Gene Expression in Osteogenic Cells from Rat Calvariae (2021)
  • Author(s): Shimohira Tsuyoshi、Niimi Hiromi、Ohsugi Yujin、Tsuchiya Yosuke、Morita Kazuki、Yoshida Sumiko、Hatasa Masahiro、Shiba Takahiko、Kadokura Hiroshi、Yokose Satoshi、Katagiri Sayaka、Iwata Takanori、Aoki Akira
  • Journal Title: Photobiomodulation, Photomedicine, and Laser Surgery Volume: 39 Issue: 8 Pages: 566-577
  • DOI: 10.1089/photob.2020.4958
  • Peer Reviewed
• [Journal Article] 低出力Er:YAGレーザーのPhotobiomodulationに対する歯周組織の細胞学的応答 (2021)
  • Author(s): 新見ひろみ、大杉勇人、片桐さやか、土谷洋輔、畑佐将宏、下平剛、門倉弘志、横瀬敏志、岩田隆紀、青木章
  • Journal Title: 日本レーザー歯学会誌 Volume: 31 Pages: 53-57
  • NAID: 130008080823
• [Journal Article] The key royal jelly component 10-hydroxy-2-decenoic acid protects against bone loss by inhibiting NF-κB signaling downstream of FFAR4 (2020)
  • Author(s): Tsuchiya Yosuke、Hayashi Mikihito、Nagamatsu Katashi、Ono Takehito、Kamakura Masaki、Iwata Takanori、Nakashima Tomoki
  • Journal Title: Journal of Biological Chemistry Volume: 295 Issue: 34 Pages: 12224-12232
  • DOI: 10.1074/jbc.ra120.013821
  • Peer Reviewed / Open Access
• [Presentation] 結紮誘導歯周炎モデルマウスを用いたダイオードレーザー照射による歯周炎抑制効果 (2021)
  • Author(s): 大杉勇人、畑佐将宏、下平剛、芝多佳彦、駒津匡二、土谷洋輔、福場駿介、新見ひろみ、森田和機、片桐さやか、岩田隆紀、青木章
  • Organizer: 第33回 日本レーザー歯学会学術大会
• [Presentation] Porphyromonas gingivalisは妊娠中の母体の肥満と胎仔の低体重を引き起こす (2021)
  • Author(s): 吉田澄子、片桐さやか、畑佐将宏、大杉勇人、土谷洋輔、新見ひろみ、下平剛、劉安豪、森田和機、佐々木直樹、前川祥吾、芝多佳彦、新田浩、岩田隆紀
  • Organizer: 第64回秋季日本歯周病学会学術大会
• [Presentation] Low-Level Er:YAG laser irradiation induced alteration of gene expression in rat calvarial osteogenic cells. (2021)
  • Author(s): Shimohira T, Niimi H, Ohsugi Y, Tsuchiya Y, Morita K, Yoshida S, Hatasa M, Shiba T, Kadokura H, Yokose S, Katagiri S, Iwata T, Aoki A.
  • Organizer: Dental Laser Virtual Scientific Conference 2021