The role of the histone methyltransferase G9a during tendon formation

• Project/Area Number: 16K11797
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Tsurumi University
• Principal Investigator: Wada Satoshi 鶴見大学, 歯学部, 助教 (20581119)
• Co-Investigator(Kenkyū-buntansha): 二藤 彰 鶴見大学, 歯学部, 教授 (00240747) ; 島田 明美 鶴見大学, 歯学部, 講師 (00339813) ; 中村 芳樹 鶴見大学, 名誉教授, 名誉教授 (10097321)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: エピジェネティクス / ヒストンメチル化 / 腱組織 / 発生 / ヒストンメチル化酵素 / 腱細胞分化

Outline of Final Research Achievements

In this study, we investigated the functions of G9a in tendon development using G9a conditional knockout (cKO) mice. G9a cKO mice showed hypoplastic tendons compared with control mice. Immunohistochemical analysis revealed that expression of type I collagen was expressed lower in vertebral tendon tissue of G9a cKO mice than in that of control. BrdU labeling revealed that proliferation rates decreased in tenocytes of G9a cKO mice
These results indicate that G9a regulates proliferation and differentiation of tendon during tendon development.

Academic Significance and Societal Importance of the Research Achievements

腱組織および歯根膜組織の細胞は共通のマーカー分子を多く発現しており、それらの遺伝子が過剰な石灰化を制御し、恒常性の維持を行っていると考えられる。本研究により、ヒストンメチル化酵素による腱関連遺伝子の制御機構を明らかにすることにより、腱組織の異所性石灰化や歯根膜組織の骨性癒着の原因および今まで困難であった腱・歯根膜組織の修復および再生機序が解明されることが期待できる。

Research Products

• [Journal Article] Single Local Injection of Epigallocatechin Gallate-Modified Gelatin Attenuates Bone Resorption and Orthodontic Tooth Movement in Mice (2018)
  • Author(s): Katsumata, Yuta Kanzaki, Hiroyuki Honda, Yoshitomo Tanaka, Tomonari Yamaguchi, Yuuki Itohiya, Kanako Fukaya, Sari Miyamoto, Yutaka Narimiya, Tsuyoshi Wada, Satoshi Nakamura, Yoshiki
  • Journal Title: Polymers Volume: 10 Issue: 12 Pages: 1384-1384
  • DOI: 10.3390/polym10121384
  • Peer Reviewed / Open Access
• [Journal Article] Annexin A5 involvement in bone overgrowth at the enthesis (2018)
  • Author(s): Shimada Akemi, Ideno Hisashi, Arai Yoshinori, Komatsu Koichiro, Wada Satoshi, Yamashita Teruhito, Amizuka Norio, Poschl Ernst, Brachvogel Bent, Nakamura Yoshiki, Nakashima Kazuhisa, Mizukami Hiroaki, Ezura Yoichi, Nifuji Akira
  • Journal Title: Journal of Bone and Mineral Research Volume: 印刷中 Issue: 8 Pages: 1532-1543
  • DOI: 10.1002/jbmr.3453
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dimethyl fumarate inhibits osteoclasts via attenuation of reactive oxygen species signaling by augmented anti oxidation (2018)
  • Author(s): Yamaguchi Y, Kanzaki H, Katsumata Y, Itohiya K, Fukaya S, Miyamoto Y, Narimiya T, Wada S, Nakamura Y
  • Journal Title: Journal of Cellular and Molecular Medicine Volume: 22 Issue: 2 Pages: 1138-1147
  • DOI: 10.1111/jcmm.13367
  • Peer Reviewed / Open Access
• [Journal Article] Asporin stably expressed in the surface layer of mandibular condylar cartilage and augmented in the deeper layer with age (2017)
  • Author(s): Miyamoto Y, Kanzaki H, Wada S, Tsuruoka S, Itohiya K, Kumagai K, Hamada Y, Nakamura Y
  • Journal Title: Bone Reports Volume: 7 Pages: 41-50
  • DOI: 10.1016/j.bonr.2017.07.002
  • Peer Reviewed / Open Access
• [Journal Article] Pathways that regulate ROS scavenging enzymes, and their role in defense against tissue destruction in periodontitis (2017)
  • Author(s): Kanzaki H, Wada S, Narimiya T, Yamaguchi Y, Katsumata Y, Itohiya K, Fukaya S, Miyamoto Y, Nakamura Y
  • Journal Title: Frontiers in Physiology Volume: 8
  • DOI: 10.3389/fphys.2017.00351
  • Peer Reviewed / Open Access
• [Journal Article] Orthodontic tensile strain induces angiogenesis via type IV collagen degradation by matrix metalloproteinase-12 (2017)
  • Author(s): Narimiya, T. Wada, S. Kanzaki, H. Ishikawa, M. Tsuge, A. Yamaguchi, Y. Nakamura, Y.
  • Journal Title: J Periodontal Res Volume: 印刷中 Issue: 5 Pages: 1-11
  • DOI: 10.1111/jre.12453
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Novel device for application of continuous mechanical tensile strain to mammalian cells (2017)
  • Author(s): Wada, Satoshi Kanzaki, Hiroyuki Narimiya, Tsuyoshi Nakamura, Yoshiki
  • Journal Title: Biology Open Volume: 6 Pages: 518-524
  • DOI: 10.1242/bio.023671
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] RANKL induces Bach1 nuclear import and attenuates Nrf2-mediated antioxidant enzymes, thereby augmenting intracellular reactive oxygen species signaling and osteoclastogenesis in mice. (2017)
  • Author(s): Kanzaki H, Shinohara F, Itohiya K, Yamaguchi Y, Katsumata Y, Matsuzawa M, Fukaya S, Miyamoto Y, Wada S, Nakamura Y
  • Journal Title: FASEB J Volume: 31 Issue: 2 Pages: 781-792
  • DOI: 10.1096/fj.201600826r
  • Peer Reviewed / Open Access
• [Journal Article] A-Disintegrin and Metalloproteinase(ADAM) 17 Enzymatically Degrades Interferon-gamma (2016)
  • Author(s): Kanzaki H., Shinohara F., Suzuki M., Wada S., Miyamoto Y., Yamaguchi Y., Katsumata Y., Makihira S., Kawai T., Taubman MA, Nakamura Y.
  • Journal Title: Sci Rep Volume: 30 Issue: 1
  • DOI: 10.1038/srep32259
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular regulatory mechanisms of osteoclastogenesis through cytoprotective enzymes (2016)
  • Author(s): Kanzaki, H. Shinohara, F. Kanako, I. Yamaguchi, Y. Fukaya, S. Miyamoto, Y. Wada, S. Nakamura, Y.
  • Journal Title: Redox Biol Volume: 8 Pages: 186-191
  • DOI: 10.1016/j.redox.2016.01.006
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 腱組織形成におけるヒストンメチル化酵素G9aの機能 (2016)
  • Author(s): 和田悟史、出野尚、島田明美、上運天太一、中村芳樹、中島和久、木村宏、眞貝洋一、立花誠、二藤彰
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-11-30
• [Presentation] ヒストンメチル化酵素G9aは腱組織の正常な発生に必要である (2016)
  • Author(s): 和田悟史、出野尚、島田明美、上運天太一、中村芳樹、中島和久、木村宏、眞貝洋一、立花誠、二藤彰
  • Organizer: 第58回歯科基礎医学会学術大会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2016-08-24