Analysis of 3-D cultured dental pulp cells and osteoblasts and their clinical application

2012 Fiscal Year Final Research Report

• Project/Area Number: 22659343
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Conservative dentistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: KAWASHIMA Nobuyuki 東京医科歯科大学, 大学院・医歯学総合研究科, 助教 (60272605)
• Project Period (FY): 2010 – 2012
• Keywords: 歯髄細胞 / 骨芽細胞 / 象牙芽細胞 / 細胞分化 / 硬組織形成 / 三次元培養

Research Abstract

Dental pulp cells are differentiate into odontoblasts, which are dentin-forming cells, and osteoblasts are bone tissue-forming cells. These cells are categorized as hard tissue forming cells, and may possess common properties. Mineralization of these cells in the conventional two dimensional culture is only observed in the presence of mineralization-inducing factors, such as BMPs or ascorbic acid and beta-glycerophosphate. We revealed that three dimensional (3-D) culture induced up-regulation of odonto-/osteo-blast marker expression in dental pulp cells and osteoblasts. Transplantation of 3-D cultured pulp cells or osteoblasts into bone cavities effectively induced hard tissue formation. Clinical application of 3-D cultured dental pulp cells or osteoblasts are expected.

Research Products

• [Journal Article] Kinetics of Th17-related cytokine expression in experimentally induced rat periapical lesions (2013)
  • Author(s): S Wei, N Kawashima, N Suzuki, J Xu, S Takahashi, M Zhou, Y Koizumi, H Suda
  • Journal Title: Aust Endod J Volume: (in press)
  • DOI: doi:10.1111/j.1747-4477.2012.00371.x
• [Journal Article] A new horizon for tissue regeneration? (2012)
  • Author(s): Kawashima N. Characterisation of dental pulp stem cells
  • Journal Title: Arch Oral Biol. Volume: 57 Pages: 1439-58
  • DOI: doi:10.1016/j.archoralbio.2012.08.010
• [Journal Article] Promotional effects of vasoactive intestinal peptide on the development of rodent Hertwig's epithelial root sheath (2012)
  • Author(s): J Xu, N Kawashima, N Fujiwara, H Harada, MS. Ota, H Suda
  • Journal Title: Congenital Anomalies Volume: Volume 52, Issue 3 Pages: 162-167
  • DOI: doi:10.1111/j.1741-4520.2012.00371.x.
• [Journal Article] Comparison of gingiva, dental pulp, and periodontal ligament cells from the standpoint of mesenchymal stem cellproperties (2012)
  • Author(s): Koji Otabe, Takeshi Muneta, Nobuyuki Kawashima, Hideaki Suda, Kunikazu Tsuji, Ichiro Sekiya
  • Journal Title: Cell Medicine Volume: Vol. 4 Pages: 13-21
• [Journal Article] Requirement of Integrin s3 for IronTransportation during Enamel Formation (2012)
  • Author(s): T. Yoshida, Y. Kumashiro, T. Iwata, J. Ishihara, T. Umemoto, Y. Shiratsuchi, N. Kawashima, T. Sugiyama, M. Yamato and T. Okano
  • Journal Title: J DENT RES published online
• [Journal Article] MEPE Activated by Furin Promotes Pulpal Cell Adhesion (2011)
  • Author(s): H.G. Wang, N. Kawashima, T. Iwata, J. Xu, S. Takahashi, T. Sugiyama, H. Suda
  • Journal Title: Jouranal of Dental Research Volume: 90(4) Pages: 529-534
  • DOI: doi:10.1177/0022034510391057
• [Journal Article] Osteogenic differentiation of mouse mesenchymal progenitor cell, Kusa-A1 is promoted by mammalian transcriptional repressor (2010)
  • Author(s): S. Wang, N. Kawashima, K. Sakamoto, K. Katsube, A. Umezawa, H Suda
  • Journal Title: Rbpj Biochemical and Biophysical Research Communications Volume: 400 Pages: 39-45
  • URL: http://dx.doi.org/10.1016/j.bbrc.2010.07.133
• [Journal Article] Differentiation of Odontoblasts Is Negatively Regulated by MEPE via Its C-Terminal Fragment (2010)
  • Author(s): H.G. Wang, N. Kawashima , T. Iwata, J. Xu, S. Takahashi, T. Sugiyama, H. Suda
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 398 Pages: 406-12
  • URL: http://dx.doi.org/10.1016/j.bbrc.2010.06.085
• [Journal Article] Expression of Notch-Signalling-related Genes in Normal and Differentiating Rat Dental Pulp Cells (2010)
  • Author(s): Sun H, Kawashima N, Xu J, TakahashiS, Suda H
  • Journal Title: Austrarian Endodontic Journal Volume: 36 Pages: 54-8
  • DOI: doi:10.1111/j.1747-4477.2009.00188.x
• [Presentation] Induction of Mineralization by Spheroid Cultured-Dental Pulp Stem Cells (2012)
  • Author(s): KAWASHIMA Nobuyuki, YAMAMOTO Mioko, SAITO Masahiro, TAKIMOTO Koyo, ZHOU Mengyu, KOIZUMI Yu, SUZUKI Noriyuki and SUDA Hideaki
  • Organizer: 日本歯科保存学会秋季大会(イングリッシュセッション)
  • Place of Presentation: 広島国際会議場
  • Year and Date: 2012-11-22
• [Presentation] Osteoblast differentiation was negativelyregulated by periostin (2012)
  • Author(s): Kawashima N, Mengyu Z, Katsube K, Kudo A, Suda H
  • Organizer: IADR 90th General Session
  • Place of Presentation: Iguacu Falls, Brazil
  • Year and Date: 2012-06-20
• [Presentation] Effects of 3-D Spheroid Culture on DentalPulp Cells (2012)
  • Author(s): M. YAMAMOTO, N. KAWASHIMA, Y. KOIZUMI, K. TAKIMOTO, M. SAITO, H. HARADA, and H. SUDA
  • Organizer: IADR 90th General Session
  • Place of Presentation: Iguacu Falls, Brazil
  • Year and Date: 2012-06-20
• [Presentation] Effects of MMP-3 on Mediator Synthesis and Accumulation of Inflammatory Cells (2012)
  • Author(s): K. Takimoto, N. Kawashima, N. Suzuki, M. Nakashima, H. Suda
  • Organizer: AAE 2012 Annual Session
  • Place of Presentation: Boston, MA
  • Year and Date: 2012-04-20
• [Presentation] Involvement of a Myogenic TranscriptionalFactor in Odontoblast Differentiation (2012)
  • Author(s): N. Kawashima, J. Xu, N. Suzuki, M. Zhou, K. Takimoto, Y. Koizumi, M. Yamamoto, H. Suda
  • Organizer: AAE 2012 Annual Session
  • Place of Presentation: Boston, MA
  • Year and Date: 2012-04-20
• [Presentation] Regulation of Periapical Bone Destructionby Cathepsin K Inhibitor (2012)
  • Author(s): N. Suzuki, N. Kawashima, K. Takimoto, H. Suda
  • Organizer: AAE 2012 Annual Session
  • Place of Presentation: Boston, MA
  • Year and Date: 2012-04-20
• [Presentation] Mechanisms of Bone Destruction and its Regulation in the Periapical Lesions (2011)
  • Author(s): Suzuki N, Kawashima N, Suda H
  • Organizer: KACD
  • Place of Presentation: Kim Koo Museum, Seoul.
  • Year and Date: 20111111-12
• [Presentation] Down-regulation of Inflammatory Mediator Synthesis from macrophages by MMP3 (2011)
  • Author(s): N Kawashima, K Takimoto, Y Koizumi, M Yamamoto, M Zhou, N Suzuki, M Nakashima, H Suda
  • Organizer: KACD
  • Place of Presentation: Kim Koo Museum, Seoul.
  • Year and Date: 20111111-12
• [Presentation] Shh and Wnt Signaling in AmeloblastDifferentiation (2011)
  • Author(s): S Takahashi, N Kawashima, K Katsube, T Sugiyama, H Sida
  • Organizer: ESE
  • Place of Presentation: CavalieriHotel, Rome.
  • Year and Date: 20110915-17
• [Presentation] Mineralization of Odonotoblastic-Lineage Cells Was Accelerated by Enhanced Expression of Mef2c (2011)
  • Author(s): N Kawashima, J Xu, N Suzuki, M Zhou, K Takimoto, Y Koizumi, M Yamamoto, S Takahashi, T Sugiyama, H Suda
  • Organizer: ESE
  • Place of Presentation: CavalieriHotel, Rome.
  • Year and Date: 20110915-17
• [Presentation] 単層培養法と三次元培養法における歯髄細胞の象牙芽細胞分化について (2011)
  • Author(s): 山本弥生子、川島伸之、須田英明
  • Organizer: 日本歯科保存学会秋季大会(第135回)
  • Place of Presentation: 大阪国際交流センター
  • Year and Date: 2011-10-20
• [Presentation] ペリオスチンによる骨芽細胞分化制御 (2011)
  • Author(s): 川島伸之、周夢宇、須田英明、工藤明、勝部憲一
  • Organizer: 日本歯科保存学会秋季大会(第135回)
  • Place of Presentation: 大阪国際交流センター
  • Year and Date: 2011-10-20
• [Presentation] Mechanisms of Bone Destruction in the Periapical Lesions and Its Regulation (2011)
  • Author(s): Kawashima N, Suzuki N, Suda H
  • Organizer: The16th Scientific Meeting of Asian Pacific Endodontic Confederation
  • Place of Presentation: Jahad Daneshgahi Complex, Shiraz, Iran
  • Year and Date: 2011-04-21
• [Presentation] Expression of Mef2c in Murine Odontoblsts (2010)
  • Author(s): N Kawashima, J Xu, N Suzuki, M Zhou, K Takimoto, Y Koizumi, M Yamamoto, A Salima, S Takahashi, H Suda
  • Organizer: 8th World Endodontic Congress
  • Place of Presentation: in Athens, Greece.
  • Year and Date: 20101006-09
• [Presentation] Shh Signaling is Related to BMP and WntSignaling in Ameloblast Differentiation (2010)
  • Author(s): S Takahashi, N Kawashima, K Katsube, T Sugiyama, H Sida
  • Organizer: 8th World Endodontic Congress
  • Place of Presentation: in Athens, Greece
  • Year and Date: 20101006-09
• [Presentation] Wnt Signaling in Odontoblast Differentiation Induced by BMP (2010)
  • Author(s): Y Koizumi, N Kawashima, K Takimoto, S Takahashi, J Xu, N Suzuki, M Zhou, M Yamamoto, A Salima, T Sugiyama, H Suda
  • Organizer: 8th World Endodontic Congress
  • Place of Presentation: in Athens, Greece
  • Year and Date: 20101006-09
• [Presentation] Analysis of osteoblastic mesenchymal cell adhesion on laser-induceddentin modification (2010)
  • Author(s): Gombo Bolortuya, Arata Ebihara, Satoshi Watanabe, Tomoo Anjo, Chizuko Kokuzawa, Hidetoshi Saegusa, Nobuyuki Kawashima, and Hideaki Suda
  • Organizer: 8th World Endodontic Congress
  • Place of Presentation: in Athens, Greece
  • Year and Date: 20101006-09
• [Presentation] Promotive effects of Sp7 on Dsppexpression (2010)
  • Author(s): N Kawashima, J Xu, T Iwata, S Takahashi, Y Koizumi, K Takimoto, Z Mengyu, C Ohi, N Suzuki, T Sugiyama, H Suda
  • Organizer: 89th IADR General Session & Exhibition
  • Place of Presentation: in Barcelona, Spain
  • Year and Date: 20100714-17
• [Presentation] Effects of MMP-3 on InflammatoryMediator Synthesis from Macrophages (2010)
  • Author(s): K Takimoto, N Kawashima, M Nakashima, H Nakamura, Y Koizumi, and H Suda
  • Organizer: 89th IADR General Session & Exhibition
  • Place of Presentation: in Barcelona, Spain
  • Year and Date: 20100714-17
• [Presentation] Effective suppression of periapical lesion expansion by Cathepsin K inhibitor (2010)
  • Author(s): Suzuki N, Kawashima N, Xu J, Suda H.
  • Organizer: 89th IADR General Session & Exhibition
  • Place of Presentation: in Barcelona, Spain
  • Year and Date: 20100714-17
• [Presentation] Expression of Vasoactive Intestinal PeptideReceptors in HERS Cells (2010)
  • Author(s): J Xu, N Kawashima, N Fujiwara, H Harada, H Suda
  • Organizer: 89th IADR General Session & Exhibition
  • Place of Presentation: in Barcelona, Spain
  • Year and Date: 20100714-17
• [Presentation] Induction of IL17 synthesis in the experimentally-induced murine periapical lesions (2010)
  • Author(s): Kawashima N., Xu J., Suzuki N., Zhou M., Wei S., Takimoto K., Koizumi Y., Takahashi S., Suda H.
  • Organizer: 2010 Spring Scientific Meeting of KoreanAcademy of Endodontics
  • Place of Presentation: BEXCO Busan, Korea
  • Year and Date: 2010-03-27
• [Presentation] 須田英明象牙芽細胞分化における Sp7 による dentin sialophosphoprotein 発現誘導 (2010)
  • Author(s): 川島伸之、許セイ、岩田隆紀、周夢宇、瀧本晃陽、小泉悠、大井智恵、高橋里美、鈴木規元
  • Organizer: 日本再生医療学会
  • Place of Presentation: 広島国際会議場
  • Year and Date: 2010-03-18