Feasibility of Molecularly Targeted Therapy for Tooth Regeneration

• Project/Area Number: 25463081
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Kyoto University
• Principal Investigator: Takahashi Katsu 京都大学, 医学(系)研究科(研究院), 准教授 (90314202)
• Co-Investigator(Kenkyū-buntansha): BESSHO Kazuhisa 京都大学, 大学院医学研究科, 教授 (90229138) ; SHIMIZU Akira 京都大学, 大学院医学研究科, 教授 (00162694) ; SUGAI MANABU 福井大学, 大学院医学研究科, 教授 (90303891)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 歯の再生 / 歯数制御 / 分子標的治療 / USAG-1 / Runx2 / CEBP/β / 過剰歯 / 先天性無歯症 / BMP-7 / C/EBPβ / BMP7 / ゼラチンスポンジ

Outline of Final Research Achievements

Human teeth are diphyodont excepting the permanent molars. The number of teeth is usually strictly determined. A number of mouse mutants provide insights into the supernumerary tooth formation. The rescue of tooth formation in genetically defined mouse models clearly demonstrates the feasibility of inducing de novo tooth formation via the in situ repression of a single targeted gene. Our investigations and related studies clearly validate the hypothesis that the de novo repression of target genes could be used to stimulate arrested tooth germs in order to induce new tooth formation in mammals. Molecular targeted therapy is a type of treatment in which drugs or other substances are used to specifically attack certain cell types by interfering with critical target molecules.
Molecularly targeted therapy seems to be a suitable approach in tooth regeneration.

Research Products

• [Journal Article] Numb chin syndrome as initial manifestation of bisphosphonate-related osteomyelitis of the jaw and methotrexate-associated lymphoproliferative disorders: a rare case (2016)
  • Author(s): Mishima, S., Takahashi, K., Tomioka, T., Bessho, K
  • Journal Title: Br J Oral Maxillofac Surg Volume: 54 Issue: 1 Pages: 114-115
  • DOI: 10.1016/j.bjoms.2015.10.031
  • Peer Reviewed
• [Journal Article] Significant association of periodontal disease with anti-citrullinated peptide antibody in a Japanese healthy population-the Nagahama study. (2015)
  • Author(s): C Terao, K Asai; M Hashimoto; T Yamazaki; K Ohmura; A Yamaguchi; K Takahashi; N Takei; T Ishii; T Kawaguchi; Y Tabara; M Takahashi; T Nakayama; S Kosugi; A Sekine; T Fujii; R Yamada; T Mimori; F Matsuda; K Bessho, Nagahama Study Group.
  • Journal Title: Journal of Autoimmunity Volume: 59 Pages: 85-90
  • DOI: 10.1016/j.jaut.2015.03.002
  • NAID: 120005601013
  • Peer Reviewed / Open Access
• [Journal Article] ANKH Polymorphisms and Clicking of the Temporomandibular Joint in Dental Residents. (2015)
  • Author(s): Huang B, Takahashi K, Goto T, Kiso H, Sugai M, Shimizu A, Kosugi S, Bessho K.
  • Journal Title: J Maxillofac Oral Surg Volume: 14 Issue: 2 Pages: 247-51
  • DOI: 10.1007/s12663-014-0622-z
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Discrepancy between chronological age and evaluated dental age using the Demirjian System in Western Australian children (2015)
  • Author(s): Wang, Mike; Huang, Boyen; Chiu, Allison; Lam, Wei-Mun; Takahashi, Katsu; Bessho, Kazuhisa; Abbott, Paul
  • Journal Title: Aust J Foren Sci Volume: 47 Issue: 4 Pages: 469-474
  • DOI: 10.1080/00450618.2014.998280
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] nfluence of non-orthodontic intervention on digit sucking and consequent anterior open bite: a preliminary study (2015)
  • Author(s): Huang B, Lejarraga C, Pumtang-on P, Franco CS, Kang Y, Lee A, Abbott J, Takahashi K, Bessho K, Sandham A
  • Journal Title: Int Dent J Volume: 65 Issue: 5 Pages: 235-241
  • DOI: 10.1111/idj.12178
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Application of anti-BMP antibodies to immunohistochemical examination of fibrous dysplasia (2015)
  • Author(s): Kiso, H., Takahashi, K., Kang, Y., Sakata-Goto, T., Huang, B., Tsukamoto, H. Nakashima, Y. and Bessho, K
  • Journal Title: J Oral Maxillofac Surg Med Path, Volume: 27 Pages: 106-111
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mitochondrial function provides instructive signals for activation-induced B cell fates (2015)
  • Author(s): Kyoung-Jin Jang, Hiroto Mano, Koji Aoki, Tatsunari Hayashi, Yukiko Nambu, Eri Hara, Katsu Takahashi, Katsuhiko Itoh, Shigeru Taketani, Kazuhiko Igarashi, Akira Shimizu and Manabu Sugai
  • Journal Title: Nature Commun Volume: 6 Issue: 1 Pages: 6750-6750
  • DOI: 10.1038/ncomms7750
  • NAID: 120005595832
  • Peer Reviewed / Open Access
• [Journal Article] Interactions between BMP-7 and USAG-1 (Uterine Sensitization-Associated Gene-1) Regulate Supernumerary Organ Formations (2014)
  • Author(s): Honoka Kiso, Katsu Takahashi , Kazuyuki Saito, Yumiko Togo, Hiroko Tsukamoto, Boyen Huang, Manabu Sugai, Akira Shimizu, Yasuhiko Tabata, Aris N. Economides, Harold C. Slavkin, Kazuhisa Bessho
  • Journal Title: PlosOne Volume: 9 Issue: 5 Pages: 96938-96944
  • DOI: 10.1371/journal.pone.0096938
  • Peer Reviewed / Open Access
• [Journal Article] Prospective signs of cleidocranial dysplasia in Cebpb deficiency (2014)
  • Author(s): Boyen Huang1,2, Katsu Takahashi2*, Ernest A Jennings1 , Pongthorn Pumtang-on3 , Honoka Kiso2 , Yumiko Togo2 , Kazuyuki Saito2 , Manabu Sugai4 , Shizuo Akira5 , Akira Shimizu4 and Kazuhisa Bessho2
  • Journal Title: Journal of Biomedical Science Volume: 21 Issue: 1 Pages: 44-48
  • DOI: 10.1186/1423-0127-21-44
  • Peer Reviewed / Open Access
• [Journal Article] The effect of nicotine on osteoinduction by recombinant human bone morphogenetic protein-2. (2014)
  • Author(s): Tamura, K., Togo, Y., Kaihara, S., Hussain, A., Takahashi, K., and Bessho, K.
  • Journal Title: Int J Oral Maxillofac Surg Volume: 43 Issue: 8 Pages: 1022-1029
  • DOI: 10.1016/j.ijom.2014.02.014
  • NAID: 10018954979
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Recent clinical evidence of bisphosphonate-related osteomyelitis of the jaw for the risk, prevention and treatment (2014)
  • Author(s): Yamazaki, T., Takahashi, K., Bessho, K.
  • Journal Title: Reviews on Recent Clinical Trials Volume: 9 Pages: 37-52
  • Peer Reviewed / Open Access
• [Journal Article] An association between anti-nuclear antibodies and HLA class II locus and heterogeneous characteristics of staining patterns: The Nagahama Study. (2014)
  • Author(s): Terao C, Ohmura K, Yamada R, Kawaguchi T, Shimizu M, Tabara Y, Takahashi M, Setoh K, Nakayama T, Kosugi S, Sekine A, Matsuda F, Tsuneyo Mimori T on behalf of the Nagahama Study Group.
  • Journal Title: Arthritis Rheumatol. Volume: 66 Issue: 3_suppl Pages: 3395-403
  • DOI: 10.1177/0022034514559127
  • Peer Reviewed / Open Access
• [Journal Article] Bone regeneration of rat calvarial defect by magnesium calcium phosphate gelatin scaffolds with or without bone morphogenetic protein-2 (2014)
  • Author(s): A. Hussain, K. Takahashi, J. Sonobe, M Bamba, Y. Tabata, K. Bessho
  • Journal Title: J Maxillofac Oral Surg Volume: 13 Issue: 1 Pages: 29-35
  • DOI: 10.1007/s12663-013-0478-7
  • Peer Reviewed
• [Journal Article] Phenotypes of CCAAT/enhancer-binding protein beta deficiency: Hyperdontia and elongated coronoid process. (2013)
  • Author(s): Huang, B., Takahashi, K., Sakata-Goto, T., Kiso, H., Togo, Y., Saito, K., Tsukamoto, H., Sugai, M., Akira, S., Shimizu, A. and Bessho, K.
  • Journal Title: Oral Diseases Volume: 19 Issue: 2 Pages: 144-150
  • DOI: 10.1111/j.1601-0825.2012.01963.x
  • Peer Reviewed
• [Journal Article] Mastication and risk for diabetes in a Japanese population: a cross-sectional study. (2013)
  • Author(s): Yamazaki T, Yamori M, Asai K, Nakano-Araki I, Yamaguchi A, Takahashi K, Sekine A, Matsuda F, Kosugi S, Nakayama T, Inagaki N, Bessho K; Nagahama Study Collaboration Group.
  • Journal Title: PLoS One. Volume: 8 Issue: 6 Pages: e64113-e64113
  • DOI: 10.1371/journal.pone.0064113
  • Peer Reviewed
• [Journal Article] Assessing anteroposterior basal bone discrepancy with the Dental Aesthetic Index (2013)
  • Author(s): Huang B, Takahashi K, Yamazaki, T., Saito, K., Yamori, M.,Asai, K., Yoshikawa Y., Kamioka H.,, Yamashiro T., Bessho K
  • Journal Title: Angle Orthod Volume: 83 Issue: 3 Pages: 527-532
  • DOI: 10.2319/050312-369.1
  • Peer Reviewed
• [Journal Article] Aldehyded dextran and ε-poly(l-lysine) hydrogel as non-viral gene carrier. (2013)
  • Author(s): Togo Y, Takahashi K, Saito K, Kiso H, Huang B, Tsukamoto H, Hyon SH, Bessho K.
  • Journal Title: Stem Cell Int, Volume: 2013 Pages: 634379-634379
  • DOI: 10.1155/2013/634379
  • Peer Reviewed
• [Journal Article] Magnesium calcium phosphate / β-tricalcium phosphate incorporation into gelatin scaffold, in vitro comparative study (2012)
  • Author(s): Hussain, A., Bessho, K. Takahashi, K., and Tabata, Y
  • Journal Title: J Tissue Eng Regen M Volume: (in press) Issue: 11 Pages: 919-924
  • DOI: 10.1002/term.1596
  • Peer Reviewed
• [Presentation] エナメル上皮細胞におけるCebpβとRunx2の作用機序の解析 (2016)
  • Author(s): 斉藤和幸
  • Organizer: 第15回 日本再生医療学会
  • Place of Presentation: 大阪
  • Year and Date: 2016-03-17
• [Presentation] マウス切歯エナメル上皮細胞株におけるC/EBPβと分子機序の解析 (2015)
  • Author(s): 斎藤和幸
  • Organizer: 第60回 日本口腔外科学会総会
  • Place of Presentation: Melbourne
  • Year and Date: 2015-10-27
• [Presentation] Interaction between Bmp-7 and USAG-1 regulate formation of supernumerary maxillary incisors. (2015)
  • Author(s): Takahashi, K.
  • Organizer: The International Conference on Oral and Maxillofacial Surgery 2015
  • Place of Presentation: Melbourne
  • Year and Date: 2015-10-27
  • Int'l Joint Research
• [Presentation] 再生創薬を目指した分子標的治療による歯の再生 (2015)
  • Author(s): 高橋克
  • Organizer: 第60回 日本口腔外科学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-16
• [Presentation] 歯の再生へ向けたUSAG-1とBMP7遺伝子変異マウスにおけるエナメル上皮幹細胞の解析 (2015)
  • Author(s): 喜早ほのか
  • Organizer: 第36回 日本炎症・再生医学会
  • Place of Presentation: 東京
  • Year and Date: 2015-07-21
• [Presentation] 遺伝性歯牙欠損症に関連した，歯の再生に向けたRunx2とUSAG-1を標的遺伝子とした遺伝子欠損マウスの解析 (2014)
  • Author(s): 喜早ほのか・高橋克・ 東郷由弥子・ 斎藤和幸・ 塚本容子・ 別所和久
  • Organizer: 第５９回 日本口腔外科学会総会
  • Place of Presentation: 幕張
  • Year and Date: 2014-10-17 – 2015-10-19
• [Presentation] C/EBPβとRunx2を用いた歯の再生へ向けた基礎的研究 (2014)
  • Author(s): 斎藤和幸・ 高橋克・ 喜早ほのか・東郷由弥子・ 塚本容子・ 永田昌毅、
  • Organizer: 第５９回 日本口腔外科学会総会
  • Place of Presentation: 幕張
  • Year and Date: 2014-10-17 – 2014-10-19
• [Presentation] BMP7ヘテロマウス、USAG-1ヘテロあるいはKOマウスは歯の大きさが変化する (2013)
  • Author(s): 斎藤和幸、高橋克、喜早ほのか、東郷由弥子、塚本容子、別所和久
  • Organizer: 第６7回 日本口腔科学会
  • Place of Presentation: 宇都宮
• [Presentation] 新規BMP拮抗分子USAG-1とBMP-7の歯数制御に関する機能解析 (2013)
  • Author(s): 喜早ほのか、高橋克、坂田朋子、Huang Boyen、塚本容子、柳田素子、
  • Organizer: 第34回日本炎症・再生医学会
  • Place of Presentation: 京都
• [Book] Feasibility of Molecularly targeted therapy for tooth regeneration: New Trends in Tissue Engineering and Regenerative Medicine- Official Book of the Japanese Society of Regenerative Medicine (2015)
  • Author(s): 3.Takahashi, K., Kiso, H., Saito, K., Togo, Y., Tsukamoto, H., Huang, B. and Bessho, K.
  • Total Pages: 11
  • Publisher: In Tech
• [Book] Gene Therapy-Tools and Potential Applications (2013)
  • Author(s): 2. Takahashi, K., Kiso, H., Saito, K., Togo, Y., Tsukamoto, H., Huang, B. and Bessho, K.
  • Total Pages: 744
  • Publisher: In Tech
• [Remarks] 京都大学医学研究科口腔外科
  • URL: http://www.med.kyoto-u.ac.jp/organization-staff/research/doctoral_course/r-057/
• [Remarks] 京都大学医学部附属属病院歯科口腔外科
  • URL: http://www.kuhp.kyoto-u.ac.jp/~oral_surg/Oral_Surg_index.html
• [Remarks] 京都大学医学部附属病院歯科口腔外科
  • URL: http://kuhp.kyoto-u.ac.jp/~oral_surg/Oral_Surg_index.html
• [Remarks] 京都大学大学院医学研究科・医学部
  • URL: http://www.med.kyoto-u.ac.jp/organization-staff/research/doctoral_course/r-057/