Development of fundamental technologies to establish the system of tooth regeneration

2013 Fiscal Year Final Research Report

• Project/Area Number: 23249085
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthodontic/Pediatric dentistry
• Research Institution: Tohoku University
• Principal Investigator: TAKANO-YAMAMOTO Teruko 東北大学, 歯学研究科(研究院), 教授 (00127250)
• Co-Investigator(Kenkyū-buntansha): TAKESHITA Nobuo 東北大学, 大学院・歯学研究科, 助教 (50431515) ; IKEDA Etsuko 東北大学, 大学院・歯学研究科, 大学院非常勤講師 (20509012)
• Project Period (FY): 2011-11-18 – 2014-03-31
• Keywords: iPS細胞 / 器官原基法 / 再生医学 / 歯科

Research Abstract

In the present study, we have developed fundamental technologies to establish the system of tooth regeneration. Neural crest-like cells (NCLCs) were induced from murine iPS cells, and they were three-dimensionally constructed with epithelial tissues isolated from tooth germs. Development of regenerative teeth was observed in organ culture system. We examined induction of tooth germ cells from murine iPS cells and NCLCs. Moreover, we analyzed mechanisms that IGF-1 enlarge size of regenerative teeth. IGF-1 induced proliferation and odontoblast differentiation of mesenchymal cells isolated from tooth germs. In addition, to obtain basic notions directing the application of mechanical stresses for tooth regeneration, we examined the responses of osteocytes and cranial sutures to mechanicals stresses.

Research Products

• [Journal Article] Compressive Force-Produced CCN2 Induces Osteocyte Apoptosis Through ERK1/2 Pathway (2014)
  • Author(s): Hoshi K, Kawaki H, Takahashi I, Takeshita N, Seiryu M, Murshid SA, Masuda T, Anada T, Kato R, Kitaura H, Suzuki O, Takano-Yamamoto T
  • Journal Title: J Bone Miner Res Volume: 29 Pages: 1244-1257
  • DOI: 10.1002/jbm.2115
  • Peer Reviewed
• [Journal Article] An anti-c-Fms antibody inhibits osteoclastogenesis in a mouse periodontitis model (2014)
  • Author(s): Kimura K, Kitaura H, Fujii T, Ishida M, Hakami Z, Takano-Yamamoto T
  • Journal Title: Oral Diseases. Volume: 20(3) (in press) Pages: 319-24
  • DOI: 10.1111/odi.12117
  • Peer Reviewed
• [Journal Article] Osteocyte function under compressive mechanical force (2014)
  • Author(s): Takano-Yamamoto T
  • Journal Title: Japanese Dental Science Review Volume: 50(2) Pages: 29-39
  • DOI: 10.1016/j.jdsr.2013.10.004
  • Peer Reviewed
• [Journal Article] Effect of cytokines on osteoclast formation and bone resorption during mechanical force loading of the periodontal membrane (2014)
  • Author(s): Kitaura H, Kimura K, Ishida M, Sugisawa H, Kohara H, Yoshimatsu M, Takano-Yamamoto T
  • Journal Title: Scientific World Journal Volume: 19
  • DOI: 10.1155/2014/617032
  • Peer Reviewed
• [Journal Article] Immunological Expression of Pituitary Adenylate Cyclase-Activating Peptide (PACAP) and PAC1 in the Periodontal Ligament After Tooth Luxation (2013)
  • Author(s): Nonaka S, Kitaura H, Kimura K, Ishida M, Takano-Yamamoto T
  • Journal Title: Cell Mol Neurobiol Volume: 33(7) Pages: 885-92
  • DOI: 10.1007/s10571-013-9953-4
  • Peer Reviewed
• [Journal Article] Lectin histochemistry of palatine glands in the developing rat (2013)
  • Author(s): Hakami ZW., Kitaura, H., Honma, S., Wakisaka, S., Takano-Yamamoto T
  • Journal Title: Acta Histochemica Volume: (in press)
  • DOI: 10.1016/j.acthis.2013.11.002
  • Peer Reviewed
• [Journal Article] N-myristoylation is essential for protein phosphatases PPM1A and PPM1B to dephosphorylate their physiological substrates in cells (2013)
  • Author(s): Chida T, Ando M, Matsuki T, Masu Y, Nagaura Y, Takano-Yamamoto T, Tamura S, Kobayashi T
  • Journal Title: Biochem J Volume: 449(3) Pages: 741-9
  • DOI: 10.1042/BJ20121201
  • Peer Reviewed
• [Journal Article] Gap junction-mediated communication in human periodontal ligament cells (2013)
  • Author(s): Kato R, Ishihara Y, Kawanabe N, Sumiyoshi K, Yoshikawa Y, Nakamura M, Imai Y, Yanagita T, Fukushima H, Kamioka H, Takano-Yamamoto T and Yamashiro T
  • Journal Title: JDR Volume: 92(7) Pages: 635-40
  • DOI: 10.1177/0022034513489992
  • Peer Reviewed
• [Journal Article] Methionine adenosyltransferase II-dependent histone H3K9 methylation at the COX-2 gene locus (2013)
  • Author(s): Kera Y, Katoh Y, Ohta M, Matsumoto M, Takano-Yamamoto T, Igarashi K
  • Journal Title: J Biol Chem Volume: 288(19) Pages: 13592-601
  • DOI: 10.1074/jbc.M112.429738
  • Peer Reviewed
• [Journal Article] Immunological reaction in TNF- α-mediated osteoclast formation and bone resorption in vitro and in vivo (2013)
  • Author(s): Kitaura H, Kimura K, Ishida M, Kohara H, Yoshimatsu M, Takano-Yamamoto T
  • Journal Title: Clin Dev Immunol Volume: 2013
  • DOI: 10.1155/2013/181849
  • Peer Reviewed
• [Journal Article] Anti-c-Fms antibody inhibits lipopolysaccharide-induced osteoclastogenesis in vivo (2012)
  • Author(s): Kimura K, Kitaura H, Fujii T, Hakami Z, Takano-Yamamoto T
  • Journal Title: FEMS Immunology & Medical Microbiology Volume: 64(2) Pages: 219-227
  • DOI: 10.1111/j.1574-695X.2011.00888.x.
  • Peer Reviewed
• [Journal Article] Increase of CGRP-Containing Nerve Fibers in the Rat Periodontal Ligament After Luxation (2012)
  • Author(s): Nagayama T, Seiryu M, Deguchi T, Kano M, Suzuki T, Takano-Yamamoto T, Ichikawa H
  • Journal Title: Cell Mol Neurobiol Volume: 32(3) Pages: 391-397
  • DOI: 10.1007/s10571-011-9767-1
  • Peer Reviewed
• [Journal Article] IL-4 inhibits TNF- α-mediated osteoclast formation by inhibition of RANKL expression in TNF- α-activated stromal cells and direct inhibition of TNF- α-activated osteoclast precursors via a T-cell-independent mechanism in vivo (2012)
  • Author(s): Fujii T, Kitaura H, Kimura K, Hakami ZW, Takano-Yamamoto T
  • Journal Title: bone Volume: 51(4) Pages: 771-780
  • DOI: 10.1016/j.bone
  • Peer Reviewed
• [Journal Article] Promotion of Ccn2 expression and osteoblastic differentiation by actin polymerization, which is induced by laminar fluid flow stress (2012)
  • Author(s): Honjo T, Kubota S, Kamioka H, Sugawara Y, Ishihara Y, Yamashiro T, Takigawa M, Takano-Yamamoto T
  • Journal Title: J Cell Commun Signal Volume: 6(4) Pages: 225-32
  • DOI: 10.1007/s12079-012-0177-z.
  • Peer Reviewed
• [Journal Article] Analgesic effects of the non-nitrogen-containing bisphosphonates etidronate and clodronate, independent of anti-resorptive effects on bone (2012)
  • Author(s): Kim S, Seiryu M, Okada S, Kuroishi T, Takano-Yamamoto T, Sugawara S, Endo Y
  • Journal Title: Eur J Pharmacol Volume: 699(1 -3) Pages: 14-22
  • DOI: 10.1016/j.ejphar.2012.11.031
  • Peer Reviewed
• [Journal Article] IL-12- and IL-18-mediated nitric oxide-induced apoptosis in TNF- α-mediated osteoclastogenesis of bone marrow cells (2011)
  • Author(s): Kitaura H, Fujimura Y, Yoshimatsu M, Kohara H, Morita Y, Aonuma T, Fukumoto E, Masuyama R, Yoshida N, Takano-Yamamoto T
  • Journal Title: Calcified Tissue International Volume: 89(1) Pages: 65-73
  • DOI: 10.1007/s00223-011-9494-0.
  • Peer Reviewed
• [Journal Article] Differential roles of CCN family proteins during osteoblast differentiation : Involvement of Smad and MAPK signaling pathways (2011)
  • Author(s): Kawaki H, Kubota S, Suzuki A, Suzuki M, Kohsaka K, Hoshi K, Fujii T, Lazar N, Ohgawara T, Maeda T, Perbal B, Takano-Yamamoto T, Takigawa M
  • Journal Title: Bone Volume: 49(5) Pages: 975-989
  • DOI: 10.1016/j.bone.2011.06.033.
  • Peer Reviewed
• [Journal Article] Tsuji Functional tooth regeneration using a bioengineered tooth unit as a mature organ replacement regenerative therapy (2011)
  • Author(s): Oshima M, Mizuno M, Imamura A, Ogawa M, Yasukawa M, Yamazaki H, Morita R, Ikeda E, Nakao K, Takano-Yamamoto T, Kasugai S, Saito M
  • Journal Title: PLoS One Volume: 6(7) Pages: e21531
  • DOI: 10.1371/journal.pone.0021531.
  • Peer Reviewed
• [Journal Article] Allergy-inducing nickel concentration is lowered by lipopolysaccharide at both the sensitization and elicitation steps in a murine model (2011)
  • Author(s): Kinbara M, Sato N, Kuroishi T, Takano-Yamamoto T, Sugawara S, Endo Y
  • Journal Title: Br J Dermatol Volume: 164(2) Pages: 356-362
  • DOI: 10.1111/j.1365-2133.2010.10016.x
  • Peer Reviewed
• [Presentation] Activity of parietal somatosensory neurons during sequential tongue moter task : with special reference to the temporal structure of spike trains. Innovate Research for Biosis-Abiosis Intelligent Interface Symposium (2014)
  • Author(s): Kitaura H, Kimura K, Ishida M, Hakami ZW, Saeed J, Sugisawa H, Kohara H, Ypshimastu M, Takano-Yamamoto T
  • Organizer: The 5th International Symposium for Interface Oral Health Science
  • Place of Presentation: Sendai, Miyagi, Japan
  • Year and Date: 20140120-21
• [Presentation] M-CSF receptor c-Fms antibody inhibits pathological osteoclast formation in vivo. Innovate Research for Biosis-Abiosis Intelligent Interface Symposium (2014)
  • Author(s): Kimura K, Kitaura H, Ishida M, Hakami ZW, Saeed J, Sugisawa H, Takano-Yamamoto T
  • Organizer: The 5th International Symposium for Interface Oral Health Science
  • Place of Presentation: Sendai, Miyagi, Japan
  • Year and Date: 20140120-21
• [Presentation] Gap-junction-mediated communication in human periodontal ligament cells. Innovate Research for Biosis-Abiosis Intelligent Interface Symposium (2014)
  • Author(s): Kato R, Ishihara Y, Kawanabe N, Sumiyoshi K, Yoshikawa Y, Nakamura M, Imai Y, Yanagita T, Fukushima H, Kamioka H, Takano-Yamamoto T, Yamashiro T
  • Organizer: The 5th International Symposium for Interface Oral Health Science
  • Place of Presentation: Sendai, Miyagi, Japan
  • Year and Date: 20140120-21
• [Presentation] 牽引力はCTGFシグナルを介して頭蓋縫合における血管形成を促進する (2013)
  • Author(s): 竹下信郎,長谷川正和,佐々木紀代,関大輔,宮下俊郎,高野郁子,宮島悠旗,福野佐知子, 山本照子
  • Organizer: 第72回日本矯正歯科学会大会
  • Place of Presentation: 松本
  • Year and Date: 20131007-09
• [Presentation] Forkhead protein FoxC1 regulates chondrogenic genes expression by modulating Ihh/Gli2 signaling (2013)
  • Author(s): Yoshida M, Hata K, Takashima R, Iseki S, Takano-Yamamoto T, Nishimura R, Yoneda T
  • Organizer: The American Society for Bone and Mineral Research 2013 35th Annual Meeting
  • Place of Presentation: Baltimore, Maryland, USA
  • Year and Date: 20131004-07
• [Presentation] 圧縮力による骨細胞のアポトーシスに対するCTGF/CCN2の役割 (2013)
  • Author(s): 山本照子
  • Organizer: 第55回歯科基礎医学会学術大会
  • Place of Presentation: 岡山
  • Year and Date: 20130920-22
• [Presentation] IFN- γ inhibits TNF- α-mediated osteoclast formation in vitro and in vivo and induces apoptosis by Fas/Fas ligand interactions (2013)
  • Author(s): Kitaura H, Kimura K, Ishida M, Sugisawa H, Saeed J, Hakami ZW, Takano-Yamamoto T
  • Organizer: 8th International Workshop on Biomaterials in Interface Science. Innovative Research for Biosis-Abiosis Intelligent Interface Summer Seminar 2013
  • Place of Presentation: Zao, Miyagi, Japan
  • Year and Date: 20130829-30
• [Presentation] The transcription factor FoxC1 up-regulates PTHrP expression together with Gli2 in chondrocytes (2013)
  • Author(s): Yoshida M, Hata K, Takashima R, Iseki S, Takano-Yamamoto T, Nishimura R, Yoneda T
  • Organizer: The 2nd Joint Meeting of the International Bone and Mineral Society and The Japanese Society for Bone and Mineral Research
  • Place of Presentation: Kobe, Japan
  • Year and Date: 20130528-0601
• [Presentation] Early response of cranial sutures to in vivo tensile force loading (2013)
  • Author(s): Takeshita N, Hasegawa M, Sasaki K, Seki D, Miyashita S, Takano I, Takano-Yamamoto T
  • Organizer: The 2nd Joint Meeting of the International Bone and Mineral Society and The Japanese Society for Bone and Mineral Research
  • Place of Presentation: Kobe, Japan
  • Year and Date: 20130528-0601
• [Presentation] Tensile force induces vascular formation in cranial sutures via CTGF signaling (2013)
  • Author(s): Takeshita N, Hasegawa M, Sasaki K, Seki D, Miyashita S, Takano I, Fukuno S, Takano-Yamamoto T
  • Organizer: NIH-Tohoku University-JPSP Symposium
  • Place of Presentation: Sendai, Japan
  • Year and Date: 20130509-10
• [Presentation] The transcription factor FoxC1 regulates chondrogenesis together with Gli2 through induction of PTHrP (2013)
  • Author(s): Yoshida M, Hata K, Takashima R, Iseki S, Takano-Yamamoto T, Nishimura R, Yoneda T
  • Organizer: 第7回Bone Research Seminar
  • Place of Presentation: 東京
  • Year and Date: 20130215-16
• [Presentation] Osteocyte function under mechanical compressive force (2013)
  • Author(s): Takano-Yamamoto T
  • Organizer: NIDCR-Tohoku University Graduate School of Dentistry Symposium
  • Place of Presentation: 仙台
  • Year and Date: 2013-05-10
  • Invited
• [Presentation] Gap junction-mediated Cell-cell Communication in Human Periodontal ligament Cells (2013)
  • Author(s): Kato R, Yoshirhiro I, Kawanabe N, Sumiyoshi K, Yoshikawa Y, Nakamura M, Imai Y, Yanagita T, Fukushima H, Kamioka H, Takano-Yamamoto T, Yamashiro T
  • Organizer: NIDCR-Tohoku University Graduate School of Dentistry Symposium
  • Place of Presentation: 仙台
  • Year and Date: 2013-05-10
• [Presentation] Neutralization of Macrophage Colony-Stimulating Factor Inhibits Pathological Osteoclatstogenesis in vitro and in vivo (2013)
  • Author(s): Kimura K, Kitaura H, Zaki Weil-Hakami, Ishida M, Sugisawa H, Takano-Yamamoto T
  • Organizer: NIDCR-Tohoku University Graduate School of Dentistry Symposium
  • Place of Presentation: 仙台
  • Year and Date: 2013-05-10
• [Presentation] IL-4 Inhibits TNF-a-mediated Osteoclast Formation via a T-cell-independent Mechanism in vitro and in vivo (2013)
  • Author(s): Kitaura H,Kimura K, Zaki Weil-Hakami, Ishida M, Sugisawa H, Takano-Yamamoto T
  • Organizer: NIDCR-Tohoku University Graduate School of Dentistry Symposium
  • Place of Presentation: 仙台
  • Year and Date: 2013-05-10
• [Presentation] Tensile Force Induces Vascular Formation in Cranial Sutures Via CTGF Signaling (2013)
  • Author(s): Takeshita N, Hasegawa M, Sasaki K, Seki D, Miyashita S, Takano I, Fukuno S, Takano-Yamamoto T
  • Organizer: NIDCR-Tohoku University Graduate School of Dentistry Symposium
  • Place of Presentation: 仙台
  • Year and Date: 2013-05-10
• [Presentation] 矯正的歯の移動モデルを用いた歯根膜幹細胞ニッチの解析 (2013)
  • Author(s): 山本照子
  • Organizer: 再生医科学研究所「再生医学・再生医療の先端融合的共同研究拠点」
  • Place of Presentation: 京都
  • Year and Date: 2013-03-15
  • Invited
• [Presentation] 圧縮力負荷による骨細胞のアポトーシスへのCTGFの関与 (2012)
  • Author(s): 星健治, 高橋一郎, 益田泰輔, 鈴木誠, 加藤龍史, 鈴木治, 上岡寛, 山城隆, 山本照子
  • Organizer: 第71回日本矯正歯科学会
  • Place of Presentation: 松本
  • Year and Date: 20120916-28
• [Presentation] The transcription factor FoxC1 regulates chondrogenesis together with Gli2 through induction of PTHrP (2012)
  • Author(s): Yoshida M, Hata K, Takashima R, Iseki S, Takano-Yamamoto T, Nishimura R, Yoneda T
  • Organizer: Australian & New Zealand Bone & Mineral Society 22nd Annual Scientific Meeting in conjunction with 1st Asia-Pacific Bone and Mineral Research Meeting
  • Place of Presentation: Pan Pacific Hotel,Perth, Western Australia
  • Year and Date: 20120902-05
• [Presentation] The transcription factor FoxC1 regulates chondrogenesis together with Gli2 through induction of PTHrP (2012)
  • Author(s): Yoshida M, Hata K, Takashima R, Iseki S, Takano-Yamamoto T, Nishimura R, Yoneda T
  • Organizer: 第34回American Society for Bone and Mineral Research
  • Place of Presentation: Minneapolis,USA
  • Year and Date: 2012-10-15
• [Presentation] 機械的刺激に対する骨細胞の応答能 (2012)
  • Author(s): 山本照子
  • Organizer: 第121回日本補綴学会
  • Place of Presentation: 横浜
  • Year and Date: 2012-05-25
  • Invited
• [Presentation] Interleukin-4 inhibits tumor necrosis factor- α-mediated osteoclast formation in vivo (2011)
  • Author(s): Fujii T, Kitaura H, Kimura K, Hakami Z, Takano-Yamamoto T
  • Organizer: The 4th International Congress and the 70th Annual Meeting of the Japanese Orthodontic Society
  • Place of Presentation: 名古屋
  • Year and Date: 20111018-20
• [Presentation] Anti-c-Fms antibody inhibits lipopolysaccharide-induced osteoclastogenesis in vivo.marrow cells in TNF- α-induced osteoclast formation (2011)
  • Author(s): Kimura K, Kitaura H, Fujii T, Hakami Z, Takano-Yamamoto T
  • Organizer: The 4th International Congress and the 70th Annual Meeting of the Japanese Orthodontic Society
  • Place of Presentation: 名古屋
  • Year and Date: 20111018-20
• [Presentation] IL-12- and IL-18-mediated nitric oxide-induced apoptosis in TNF- α-mediated osteoclastogenesis (2011)
  • Author(s): Kitaura H, Fujimura Y, Yoshimatsu M, Kohara H, Morita Y, Aonuma T, Fukumoto E, Yoshida N, Takano-Yamamoto T
  • Organizer: The 4th International Congress and the 70th Annual Meeting of the Japanese Orthodontic Society
  • Place of Presentation: Nagoya, Japan
  • Year and Date: 20111018-20
• [Patent(Industrial Property Rights)] IGFを含む成長因子による歯, 再生歯および再生歯胚における歯冠および咬頭ならびに歯根の大きさおよび形の制御の方法 (2013)
  • Inventor(s): 山本照子, 池田悦子
  • Industrial Property Rights Holder: 国立大学法人東北大学
  • Industrial Property Rights Type: PCT 国際出願
  • Industrial Property Number: PCT/JP2013/72483
  • Filing Date: 2013-08-22
  • Overseas
• [Patent(Industrial Property Rights)] IGFを含む成長因子による歯,再生歯および再生歯胚における歯冠および咬頭ならびに歯根の大きさおよび形の制御の方法 (2012)
  • Inventor(s): 山本照子, 池田悦子
  • Industrial Property Rights Holder: 国立大学法人東北大学, 日本ケミカルリサーチ
  • Industrial Property Rights Type: 特願
  • Industrial Property Number: 2012-184656
  • Filing Date: 2012-08-23