Analysis of stress-induced senescent cells to elucidate the unknown inhibitory mechanism of bone formation

• Project/Area Number: 18H02986
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 57040:Regenerative dentistry and dental engineering-related
• Research Institution: Osaka Dental University
• Principal Investigator: HONDA Yoshitomo 大阪歯科大学, 歯学部, 教授 (90547259)
• Co-Investigator(Kenkyū-buntansha): 橋本 典也 大阪歯科大学, 歯学部, 教授 (20228430) ; 片岡 宏介 徳島大学, 大学院医歯薬学研究部(歯学域), 教授 (50283792) ; 田中 知成 京都工芸繊維大学, 繊維学系, 准教授 (70585695) ; 南部 隆之 大阪歯科大学, 歯学部, 講師 (80367903)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2020: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2018: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
• Keywords: 老化細胞 / 老化 / 細胞老化 / 骨 / 再生 / 生体材料 / ストレス誘導性老化 / 骨再生 / 骨形成 / カテキン / ストレス / 再生医療

Outline of Final Research Achievements

The aim of this project was to elucidate the behavior and molecular mechanisms of senescent cells and SASP-related factors that inhibit bone formation, which can be useful to develop next-generation bone regeneration therapies free from this inhibition mechanism. Our results revealed that stress-induced premature senescent cells induced by stimuli from lipopolysaccharide or material implantation can be involved in the inhibitory mechanism of bone regeneration.

Academic Significance and Societal Importance of the Research Achievements

本研究の結果、リポ多糖あるいは材料埋入によりストレス誘導性早期老化細胞が誘導され、同細胞が骨再生の阻害に関与している可能性が明らかとなった。これらの知見は、未知なる骨再生阻害メカニズムの解明に繋がりうる知見であり、関連する細胞老化随伴分泌現象因子などの解明が更に進めば、既存の治療法とは異なる新規再生医療やバイオマテリアルの開発などに道を拓くと予想される。

Research Products

• [Journal Article] A Senomorphic‐Conjugated Scaffold for Application of Senescent Cells in Regenerative Medicine (2023)
  • Author(s): Deng Wenqi、Jo Jun‐ichiro、Tanaka Tomonari、Morikuni Hidetoshi、Hashimoto Yoshiya、Matsumoto Naoyuki、Honda Yoshitomo
  • Journal Title: Advanced Therapeutics Volume: 0 Issue: 5 Pages: 2200276-2200276
  • DOI: 10.1002/adtp.202200276
  • Peer Reviewed / Open Access
• [Journal Article] Augmentation of Bone Regeneration by Depletion of Stress-Induced Senescent Cells Using Catechin and Senolytics (2020)
  • Author(s): Honda Yoshitomo、Huang Anqi、Tanaka Tomonari、Han Xiaoyu、Gao Beiyuan、Liu Haitao、Wang Xinchen、Zhao Jianxin、Hashimoto Yoshiya、Yamamoto Kazuyo、Matsumoto Naoyuki、Baba Shunsuke、Umeda Makoto
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 12 Pages: 4213-4213
  • DOI: 10.3390/ijms21124213
  • Peer Reviewed / Open Access
• [Journal Article] Sustained Release of Catechin from Gelatin and Its Effect on Bone Formation in Critical Sized Defects in Rat Calvaria (2020)
  • Author(s): Honda Y, Huang A, Zhao J, Han X, Kurushima Y, Gong Y, Kanzaki H, Katsumata Y, Yamada Y, Hashimoto Y, Matsumoto N, Baba S, Tanaka T, Umeda M
  • Journal Title: Journal of Hard Tissue Biology Volume: 29 Issue: 2 Pages: 77-84
  • DOI: 10.2485/jhtb.29.77
  • NAID: 130007833332
  • ISSN: 1341-7649, 1880-828X
  • Peer Reviewed / Open Access
• [Journal Article] Gas Permeability of Mold during Freezing Process Alters the Pore Distribution of Gelatin Sponge and Its Bone-Forming Ability (2020)
  • Author(s): Han Xiaoyu、Honda Yoshitomo、Tanaka Tomonari、Imura Kazuki、Hashimoto Yoshiya、Yoshikawa Kazushi、Yamamoto Kazuyo
  • Journal Title: Materials Volume: 13 Issue: 21 Pages: 4705-4705
  • DOI: 10.3390/ma13214705
  • Peer Reviewed / Open Access
• [Journal Article] Releasing Behavior of Lipopolysaccharide from Gelatin Modulates Inflammation, Cellular Senescence, and Bone Formation in Critical-Sized Bone Defects in Rat Calvaria (2019)
  • Author(s): Zhao J, Honda Y, Tanaka T, Hashimoto Y, Matsumoto N.
  • Journal Title: Materials Volume: 13 Issue: 1 Pages: 95-95
  • DOI: 10.3390/ma13010095
  • Peer Reviewed / Open Access
• [Presentation] ストレス誘導性老化細胞の出現を促す材料の開発と骨再生阻害機序の解明 (2021)
  • Author(s): 本田義知，Zhao Jianxin，馬場俊輔，松本尚之，橋本典也
  • Organizer: 日本歯科理工学会 近畿・中四国地方会 令和2 年度冬期セミナー
• [Presentation] ストレス誘導性老化細胞を出現させる疾患モデル構築用材料の開発と骨再生への影響 (2021)
  • Author(s): Zhao Jianxin、本田義知、Wang Xinchen、田中知成、橋本典也、松本尚之
  • Organizer: 第20回日本再生医療学会総会
• [Presentation] 凍結乾燥時に用いる鋳型の通気性がゼラチンスポンジの構造に及ぼす影響 (2021)
  • Author(s): 韓 嘯宇、本田 義知、田中 知成、Zhao Jianxin、鞏 雅楠、劉 海濤、井村 和希、橋本 典也、吉川 一志 、山本 一世
  • Organizer: 第20回日本再生医療学会総会
• [Presentation] What is stress induced cellular senescence? (2021)
  • Author(s): Yoshitomo Honda
  • Organizer: KIT International OPEN-TECH Webinar 2021
  • Int'l Joint Research / Invited
• [Presentation] 植物由来物質とストレス誘導性老化細胞の接点 (2021)
  • Author(s): 本田義知
  • Organizer: 第70回医用高分子研究会
  • Invited
• [Presentation] 生体材料埋入で誘導されるストレス誘導性老化細胞が骨形成に及ぼす影響 (2019)
  • Author(s): 本田 義知，黄 安祺，田中 知成，韓 嘯宇，Beiyuan Gao，Xinchen Wang，劉 海濤，松本 尚之，馬場 俊輔，梅田 誠
  • Organizer: 第41回日本バイオマテリアル学会大会
  • Int'l Joint Research