Elucidation of the epigenetically regulation of the phenotype of the periodontal ligament fibroblast

• Project/Area Number: 15K11356
• 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: Yoshiki Nakamura 鶴見大学, 歯学部, 教授 (10097321)
• Co-Investigator(Kenkyū-buntansha): 野田 晃司 鶴見大学, 歯学部, 臨床教授 (10148059) ; 新井 千博 鶴見大学, 歯学部, 助教 (10460221) ; 和田 悟史 鶴見大学, 歯学部, 助教 (20581119) ; 菅崎 弘幸 鶴見大学, 歯学部, 准教授 (30333826) ; 石川 美佐緒 鶴見大学, 歯学部, 助教 (90582445) ; 高野 吉郎 鶴見大学, 歯学部, 臨床教授 (90126425)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 歯根膜 / エピジェネティクス / G9a / 歯肉 / Glp / H3K9 / H3K9 metyltransferases / H3k9me1 / H3k9me2 / H3k9me3

Outline of Final Research Achievements

Epigenetical regulation of the phenotype of the periodontal ligament fibroblast was examined and compared with that of the gingival fibroblast using experimental rats. There are differences in the expression of monomethylated Histone H3K9 and dimethylated Histone H3K9, and PDL fibroblast exhibited intense expression of monomethylated Histone H3K9. Among known methyltransferases, Glp and G9a were shown difference in the expression between gingival and PDL fibroblasts. PDL fibroblasts expressed more intense Glp and G9a expression.
These data obtained by animal experiments were confirmed in the cell culture experiments using human gingival and PDL fibroblast cell lines. Then we compared gene expression using microarray, and narrowed down the candidate genes to 10, including transcription factors.

Research Products

• [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] Possible alternative treatment for mandibular asymmetry by local unilateral igf-1 injection into the mandibular condylar cavity: Experimental study in mice. (2017)
  • Author(s): Fukaya S, Kanzaki H, Miyamoto Y, Yamaguchi Y, Nakamura Y.
  • Journal Title: American journal of orthodontics and dentofacial orthopedics Volume: 152(6) Issue: 6 Pages: 820-829
  • DOI: 10.1016/j.ajodo.2017.05.023
  • Peer Reviewed / Open Access
• [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] 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] 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] Evaluation of antibacterial activity of visible light-responsive TiO2-based photocatalyst coating on orthodontic materials against cariogenic bacteria (2016)
  • Author(s): Sudo T., Imai S., Ochiai T., Kanzaki H., Morita Y., Hanada N., Nakamura Y.
  • Journal Title: Asian Pac J Dent Volume: 16 Pages: 15-22
  • Peer Reviewed / Open Access
• [Journal Article] Defining the location of the dental midline is critical for oral esthetics in camouflage orthodontic treatment of facial asymmetry (2016)
  • Author(s): Kai r., Umeki D., Sekiya T., Nakamura Y.
  • Journal Title: Am J Orthod Dentofacial Orthop Volume: 150(6) Issue: 6 Pages: 1028-1038
  • DOI: 10.1016/j.ajodo.2015.10.035
  • 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] Eary tissue reaction in the tension zone of PDL during orthodontic tooth movement (2016)
  • Author(s): Tsuge A. Noda K. Nakamura Y
  • Journal Title: Arch Oral Biol Volume: - Pages: 17-25
  • DOI: 10.1016/j.archoralbio.2016.01.007
  • Peer Reviewed / Open Access
• [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
• [Journal Article] The main occluding area in normal occlusion and mandibular prognathism (2016)
  • Author(s): Kurokawa M., Kanzaki H., Tokiwa H., Handa H., Nakaoka K., Hamada Y., Kato H., Nakamura Y
  • Journal Title: Angle Orthod Volume: 86(1) Issue: 1 Pages: 87-93
  • DOI: 10.2319/111114-807.1
  • Peer Reviewed / Open Access
• [Journal Article] Reduction in static friction by deposition of a homogeneous diamond-like carbon (DLC) coating on orthodontic brackets (2015)
  • Author(s): Shun Akaike, Tohru Hayakawa, Daishiro Kobayashi, Yuko Aono, Atsushi Hirata, Masanori Hiratsuka, Yoshiki Nakamura
  • Journal Title: Dental Materials Journal Volume: 34 Issue: 6 Pages: 888-895
  • DOI: 10.4012/dmj.2015-130
  • NAID: 130005112768
  • ISSN: 0287-4547, 1881-1361
  • Peer Reviewed / Open Access
• [Journal Article] Protective Effects of Clenbuterol against Dexamethasone-Induced Masseter Muscle Atrophy and Myosin Heavy Chain Transition (2015)
  • Author(s): Umeki D, Ohnuki Y, Mototani Y, Shiozawa K, Suita K, Fujita T, Nakamura Y, Saeki Y, Okumura S
  • Journal Title: PLoS One Volume: 10 Issue: 6 Pages: e0128263-e0128263
  • DOI: 10.1371/journal.pone.0128263
  • Peer Reviewed / Open Access
• [Journal Article] Nrf2 activation attenuates both orthodontic tooth movement and relapse. (2015)
  • Author(s): Kanzaki H, Shinohara F, Itohiya-Kasuya K, Ishikawa M, Nakamura Y.
  • Journal Title: J Dent Res Volume: 94 Issue: 6 Pages: 787-794
  • DOI: 10.1177/0022034515577814
  • Peer Reviewed / Open Access
• [Journal Article] Periostin of human periodontal ligament fibroblasts promotes migration of human mesenchymal stem cell through the αvβ3 integrin/FAK/PI3K/Akt pathway. (2015)
  • Author(s): Matsuzawa M, Arai C, Nomura Y, Murata T, Yamakoshi Y, Oida S, Hanada N, Nakamura Y.
  • Journal Title: Journal of periodontal research Volume: 印刷中 Issue: 6 Pages: 855-863
  • DOI: 10.1111/jre.12277
  • Peer Reviewed
• [Journal Article] H3K9MTase G9a is essential for the differentiation and growth of tenocytes in vitro (2015)
  • Author(s): Wada S, Ideno H, Shimada A, Kamiunten T, Nakamura Y, Nakashima K, Kimura H, Shinkai Y, Tachibana M, Nifuji A.
  • Journal Title: Histochem Cell Biol. Volume: in press Issue: 1 Pages: 13-20
  • DOI: 10.1007/s00418-015-1318-2
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] MMP12は矯正学的歯の移動時の牽引側歯根膜組織における血管網再構築に重要な役割を果たしている (2016)
  • Author(s): 成宮 毅、和田悟史、菅崎弘幸、中村芳樹
  • Organizer: 第75回日本矯正歯科学会
  • Place of Presentation: アスティ徳島(徳島県徳島市)
  • Year and Date: 2016-11-07
• [Presentation] マウスへのmyo-inositol 栄養補充による下顎骨の成長促進 (2016)
  • Author(s): 山口祐樹、菅崎弘幸、宮本 豊、糸日谷佳菜子、深谷紗吏、勝又裕太、中村芳樹
  • Organizer: 第75回日本矯正歯科学会
  • Place of Presentation: アスティ徳島(徳島県徳島市)
  • Year and Date: 2016-11-07
• [Presentation] Asporinは咬合機能低下に伴う新生歯槽骨添加における制御因子である (2016)
  • Author(s): 糸日谷佳菜子、菅崎弘幸、石川美佐緒、下田信治、中村芳樹
  • Organizer: 第75回日本矯正歯科学会
  • Place of Presentation: アスティ徳島(徳島県徳島市)
  • Year and Date: 2016-11-07
• [Presentation] Essential roles of H3K9MTase G9a during tooth development (2015)
  • Author(s): T. Kamiunten, H. Ideno, A. Shimada, Y. Nakamura, H. Kimura, M. Tachibana, K. Nakashima, A. Nifuji
  • Organizer: The American Society for Cell Biology
  • Place of Presentation: San diego convention center, USA
  • Year and Date: 2015-12-10
  • Int'l Joint Research
• [Presentation] Asporinは咬合機能低下に伴う歯根膜腔狭窄の制御因子である (2015)
  • Author(s): 糸日谷 佳菜子 、 菅崎 弘幸 、 石川 美佐緒、 下田 信治、 中村 芳樹
  • Organizer: 第74回日本矯正歯科学会
  • Place of Presentation: 福岡国際会議場(福岡市）
  • Year and Date: 2015-11-18
• [Presentation] IGF-1の顎関節局所投与による下顎骨非対称に対する治療の可能性 (2015)
  • Author(s): 深谷紗吏 菅崎弘幸 宮本 豊 山口祐希 中村芳樹
  • Organizer: 第74回日本矯正歯科学会
  • Place of Presentation: 福岡国際会議場(福岡市)
  • Year and Date: 2015-11-18
• [Presentation] Histone 3 lysine 9 methyltransferase G9a is essential for the growth and differentiation of tenocytes (2015)
  • Author(s): Satoshi Wada, Hisashi Ideno, Akemi Shimada, Taichi Kamiunten, Yoshiki Nakamura, Kazuhisa Nakashima, Hiroshi Kimura, Makoto Tachibana, Akira Nifuji
  • Organizer: American Society for Bone and Mineral Research 2015 Annual Meeting
  • Place of Presentation: Washington State Convention Centor, Seattle, Washington, USA
  • Year and Date: 2015-10-09
  • Int'l Joint Research
• [Presentation] Bach1 nuclear export attenuates osteoclastogenesis and osteoclast activation via inhibition of intracellular ROS signaling. (2015)
  • Author(s): Hiroyuki Kanzaki, Fumiaki Shinohara, Masazumi Matsuzawa, and Yoshiki Nakamura
  • Organizer: American Society for Bone and Mineral Research 2015 Annual Meeting
  • Place of Presentation: Washington State Convention Centor, Seattle, Washington, USA
  • Year and Date: 2015-10-09
  • Int'l Joint Research