Resolution of the signaling networks involved in the pulp cell differentiation and its clinical application

• Project/Area Number: 22390357
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Conservative dentistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: KAWASHIMA Nobuyuki 東京医科歯科大学, 医歯(薬)学総合研究科, 助教 (60272605)
• Co-Investigator(Kenkyū-buntansha): KATSUBE Ken-ichi 東京医科歯科大学, 大学院・医歯学総合研究科, 講師 (20233760) ; SAKAMOTO Kei 東京医科歯科大学, 大学院・医歯学総合研究科, 助教 (00302886)
• Project Period (FY): 2010-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000); Fiscal Year 2012: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2011: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2010: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
• Keywords: 歯髄 / 歯髄細胞 / 象牙芽細胞 / Notch / Periostin / 細胞分化 / シグナルネットワーク / 分化制御 / 分化促進 / 転写調節因子 / 分化誘導 / Hey1 / 分化 / 石灰化 / Sp7

Research Abstract

Losing the tooth vitality correlates to the tooth loss, this is a challenge to QOL. Strategies to keep the integrity of the pulp tissue and regenerate the new pulp tissue are hot topics. We have reported that Notch signaling is essential for differentiation of dental pulp cells. In this project, we revealed that a secretory protein, Periostin, regulated negatively the dental pulp cell differentiation into odontoblasts via notch signaling. Controlling the synthesis and production Periostin may be essential to induce the non-mineralized pulp tissue covered by the newly formed mineralized dentin.

Research Products

• [Journal Article] Periostin is a negative regulator of mineralization in the dental pulp tissue (2014)
  • Author(s): Zhou M, Kawashima N, Suzuki N, Yamamoto M, Ohnishi O, Katsube K, Tanabe H, Kudo A, Saito M, Suda H
  • Journal Title: Odontology Volume: (in press) Issue: 2 Pages: 152-9
  • DOI: 10.1007/s10266-014-0152-7
  • Peer Reviewed / Open Access
• [Journal Article] Three-dimensional spheroid culture promotes odonto/osteoblastic differentiation of dental pulp cells (2014)
  • Author(s): M Yamamoto, N Kawashima, N Takashino, Y Koizumi, K Takimoto, N Suzuki, M Saito, and H Suda
  • Journal Title: Arch Oral Biol Volume: 59 Issue: 3 Pages: 310-317
  • DOI: 10.1016/j.archoralbio.2013.12.006
  • Peer Reviewed
• [Journal Article] Down-regulation of Inflammatory Mediator Synthesis and Infiltration of Inflammatory Cells by MMP-3 in Experimentally-induced Rat Pulpitis (2014)
  • Author(s): K Takimoto, N Kawashima, N Suzuki, Y Koizumi, M Yamamoto, M Nakashima, H Suda
  • Journal Title: J Endod Volume: (in press) Issue: 9 Pages: 1404-9
  • DOI: 10.1016/j.joen.2014.04.001
  • Peer Reviewed
• [Journal Article] Wnt11 expression in rat dental pulp and promotional effects of Wnt signaling on odontoblast differentiation (2013)
  • Author(s): Y Koizumi, N Kawashima, M Yamamoto, K Takimoto, M Zhou, N Suzuki, M Saito, H Harada, H Suda
  • Journal Title: Congenital Anomalies Volume: 53 Issue: 3 Pages: 101-108
  • DOI: 10.1111/cga.12011
  • Peer Reviewed
• [Journal Article] Comparison of gingiva, dental pulp, and periodontal ligament cells from the standpoint of mesenchymal stem cell properties (2012)
  • Author(s): Otabe K, Muneta T, Kawashima N, Suda H, Tsuji K, Sekiya I
  • Journal Title: Cell Medicine (Cell Transplantation Part B) Volume: Vol. 4 Issue: 1 Pages: 13-21
  • DOI: 10.3727/215517912x639324
• [Journal Article] Requirement of Integrin s3 for Iron Transportation during Enamel Formation (2012)
  • Author(s): Yoshida T, Kumashiro Y, Iwata T, Ishihara J, Umemoto T, Shiratsuchi Y, Kawashima N, Sugiyama T, Yamato N and Okano T
  • Journal Title: J Dent Res Volume: 91(12) Issue: 12 Pages: 1154-9
  • DOI: 10.1177/0022034512462722
• [Journal Article] Characterisation of dental pulp stem cells : A new horizon for tissue regeneration? (2012)
  • Author(s): Kawashima N
  • Journal Title: Arch Oral Biol Volume: 57 Issue: 11 Pages: 1439-58
  • DOI: 10.1016/j.archoralbio.2012.08.010
  • Peer Reviewed
• [Journal Article] Kinetics of Th17-related cytokine expression in experimentally induced rat periapical lesions (2012)
  • Author(s): S Wei, N Kawashima, N Suzuki, J Xu, S Takahashi, M Zhou, Y Koizumi, H Suda
  • Journal Title: Aust Endod J Volume: epub ahead of print Issue: 3 Pages: 1-8
  • DOI: 10.1111/j.1747-4477.2012.00371.x
  • Peer Reviewed
• [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: 52 Issue: 3 Pages: 162-167
  • DOI: 10.1111/j.1741-4520.2012.00371.x
  • Peer Reviewed
• [Journal Article] Effects of Dentin Surface Modifications Treated with Er:YAG and Nd:YAG laser Irradiation on Fibroblast Cell Adhesion (2012)
  • Author(s): Bolortuya G, Ebihara A, Ichinose S, Watanabe S, Anjo T, Kokuzawa C, Saegusa H, Kawashima N, Suda H
  • Journal Title: Photomedicine and Laser Surgery Volume: 30 Issue: 2 Pages: 63-70
  • DOI: 10.1089/pho.2011.3132
  • Peer Reviewed
• [Journal Article] MEPE Activated by Furin Promotes Pulpal Cell Adhesion (2011)
  • Author(s): HG Wang, N Kawashima, T Iwata, J Xu, S Takahashi, T Sugiyama, H Suda
  • Journal Title: J Dent Res Volume: 90(4) Issue: 4 Pages: 529-534
  • DOI: 10.1177/0022034510391057
  • Peer Reviewed
• [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: In press
  • Peer Reviewed
• [Journal Article] Expression of Notch-Signalling-related Genes in Normal and Differentiating Rat Dental Pulp Cells (2011)
  • Author(s): Sun H, Kawashima N, Xu J, Takahashi S, Suda H
  • Journal Title: Austrarian Endodontic Journal Volume: 36 Pages: 54-58
  • Peer Reviewed
• [Journal Article] Osteogenic differentiation of mouse mesenchymal progenitor cell, Kusa-A1 is promoted by mammalian transcriptional repressor Rbpj, Biochem (2010)
  • Author(s): S Wang, N Kawashima, K Sakamoto, K Katsube, A Umezawa, H Suda
  • Journal Title: Biophys. Res. Commun Volume: 400 Issue: 1 Pages: 39-45
  • DOI: 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): HG Wang, N Kawashima, T Iwata, J Xu, S Takahashi, T Sugiyama, H Suda
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 398 Issue: 3 Pages: 406-12
  • DOI: 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, Takahashi S, Suda H
  • Journal Title: Aust Endod J Volume: 36 Issue: 2 Pages: 54-8
  • DOI: 10.1111/j.1747-4477.2009.00188.x
• [Journal Article] Osteogenic differentiation of mouse mesenchymal progenitor cell, Kusa-A1 is promoted by mammalian transcriptional repressor Rbpj (2010)
  • Author(s): S.Wang, N.Kawashima, K.Sakamoto, K.Katsube, A.Umezawa H Suda
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 400 Pages: 39-45
  • Peer Reviewed
• [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: 406-412
  • Peer Reviewed
• [Presentation] Regenerative endodontics-induction of bone and dental pulp tissue from dental pulp (2014)
  • Author(s): Kawashima N
  • Organizer: 平成25年度(2013)「歯・骨関連疾患のグローバル研究センター」国際総合プレゼンテーション
  • Place of Presentation: 東京医科歯科大学
  • Year and Date: 2014-01-20
• [Presentation] 歯髄幹細胞による歯髄・骨再生の現状と課題 (2013)
  • Author(s): 川島伸之
  • Organizer: 第11回口腔医科学フロンティア学術集会
  • Place of Presentation: 宮崎・青島パームビーチホテル
  • Year and Date: 2013-03-02
  • Invited
• [Presentation] Promoting effects of Wnt signaling on odontoblast differentiation (2013)
  • Author(s): Kawashima N, Koizumi Y, Yamamoto M, et.al
  • Organizer: Asian Pacific Endodontic Conference
  • Place of Presentation: Seoul, Korea
• [Presentation] 3-D Spheroid Culture Method Promotes Odonto-/Osteo-blastic Differentiation of Dental Pulp Cells (2013)
  • Author(s): Yamamoto M, Kawashima N, Suda H
  • Organizer: The 9th World Endodontic Conference
  • Place of Presentation: Tokyo
• [Presentation] 歯髄幹細胞を用いた再生医療の現状 (2013)
  • Author(s): 川島伸之
  • Organizer: 第138回日本歯科保存学会2013年春季学術大会
  • Place of Presentation: 福岡市福岡国際会議場
  • Invited
• [Presentation] スフェロイド培養による歯髄細胞の特性変化の検討 (2013)
  • Author(s): 山本弥生子、川島伸之、鈴木規元、小泉悠、瀧本晃陽、須田英明、斉藤正寛
  • Organizer: 第138回日本歯科保存学会2013年春季学術大会
  • Place of Presentation: 福岡市福岡国際会議場
• [Presentation] ヒト歯髄幹細胞の三次元培養による象牙芽細胞・骨芽細胞マーカーの変動 (2013)
  • Author(s): 川島伸之、山本弥生子、瀧本晃陽、小泉悠、鈴木規元、須田英明
  • Organizer: 第138回日本歯科保存学会2013年春季学術大会
  • Place of Presentation: 福岡市福岡国際会議場
• [Presentation] Periostin : a negative regulator of mineralization in the dental pulp tissue (2013)
  • Author(s): Kawashima N, Mengu Z, Yamamoto M, Koizumi Y, Takimoto K, Onishi K, Suzuki N, Katsube K, Saito M, Harada H, Suda H
  • Organizer: 16th ESE (European Society of Endodontology) Biennial Congress
  • Place of Presentation: Lisbon, Portugal
• [Presentation] Spheroid culture induces odonto-/osteoblastic differentiation of dental pulp cells through integrin signaling (2013)
  • Author(s): Yamamoto M, Kawashima N, Koizumi Y, Takimoto K, Onishi K, Suzuki N, Katsube K, Saito M, Harada H, Suda H
  • Organizer: 16th ESE
  • Place of Presentation: Lisbon, Portugal
• [Presentation] Stem Cell Marker Expression in the 3-D Spheroid Cultured Human Dental Pulp Stem Cells (2013)
  • Author(s): Kawashima N, Yamamoto M, Takashino N, Takimoto K, Koizumi Y, Suzuki N, Suda H
  • Organizer: The 140th Scientific meeting of KACD
  • Place of Presentation: The K Hotel & Resort, Gyeongju
• [Presentation] Induction of Mineralization by Spheroid Cultured-Dental Pulp Stem Cells (2012)
  • Author(s): Kawashima N, Yamamoto M, Takimoto K, Mengyu Z, Koizumi Y, Suzuki N, Suda H
  • Organizer: 第137回日本歯科保存学会2012年度秋季学術大会(イングリッシュセッション)
  • Place of Presentation: 広島国際会議場、広島
  • Year and Date: 2012-11-22
• [Presentation] Effects of 3-D Spheroid Culture on Dental Pulp Cells (2012)
  • Author(s): Yamamoto M, Kawashima N, Koizumi Y, Takimoto K, Saito M, Harada H and Suda H
  • Organizer: IADR 90th General Session
  • Place of Presentation: Iguacu Falls, Brazil
  • Year and Date: 2012-06-20
• [Presentation] Involvement of a Myogenic Transcriptional Factor 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] Involvement of a Myogenic Transcriptional Factor in Odontoblast Differentiation (2012)
  • Author(s): N. Kawashima, J. Xu, N. Suzuki, M. Zhou, K. Takimoto, Y. Koizumi, M. Yamamoto, H. Suda
  • Organizer: Annual Session of American Association of Endodontics
  • Place of Presentation: Boston, USA
• [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: Annual Session of American Association of Endodontics
  • Place of Presentation: Boston, USA
• [Presentation] Regulation of Periapical Bone Destruction by Cathepsin K Inhibitor (2012)
  • Author(s): N. Suzuki, N. Kawashima, K. Takimoto, H. Suda
  • Organizer: Annual Session of American Association of Endodontics
  • Place of Presentation: Boston, USA
• [Presentation] Osteoblast differentiation was negatively regulated 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
• [Presentation] Induction of Mineralization by Spheroid Cultured-Dental Pulp Stem Cells (2012)
  • Author(s): Kawashima N, Yamamoto M, Saito M, Takimoto K, Zhou M, Koizumi Y, Suzuki N, Suda H
  • Organizer: Fall Scientific Meeting of the Japanese Association of Conservative Dentistry
  • Place of Presentation: 広島国際会議場
• [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: 第135回日本歯科保存学会2011年度秋季学術大会
  • Place of Presentation: 大阪国際交流センター、大阪
  • Year and Date: 2011-10-20
• [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: 15th ESE
  • Place of Presentation: Cavalieri Hotel, Rome
• [Presentation] Mechanisms of Bone Destruction in the Periapical Lesions and Its Regulation (2011)
  • Author(s): Kawashima N, Suzuki N, Suda H
  • Organizer: The 16th Scientific Meeting of Asian Pacific Endodontic Confederation
  • Place of Presentation: Jahad Daneshgahi Complex, Shiraz, Iran
  • Invited
• [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: Scientific Meeting of the European Society of Endodontics
  • Place of Presentation: Rome, Italy
• [Presentation] Mechanisms of Bone Destruction in the Periapical Lesions and Its Regulation (2011)
  • Author(s): Kawashima N, Suzuki N, Suda H
  • Organizer: The 16th Scientific Meeting of Asian Pacific Endodontic Confederation
  • Place of Presentation: Shiraz, Iran
  • Invited
• [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: Scientific Meeting of the Korean Academy of Endodontics
  • Place of Presentation: Seoul, Korea
• [Presentation] Mechanisms of Bone Destruction and its Regulation in the Periapical Lesions (2011)
  • Author(s): Suzuki N, Kawashima N, Suda H
  • Organizer: Scientific Meeting of the Korean Academy of Endodontics
  • Place of Presentation: Seoul, Korea
• [Presentation] Shh and Wnt Signaling in Ameloblast Differentiation (2011)
  • Author(s): S Takahashi, N Kawashima, K Katsube, T Sugiyama, H Suda
  • Organizer: Scientific Meeting of the European Society of Endodontics
  • Place of Presentation: Rome, Italy
• [Presentation] 歯髄幹細胞と再生医療 (2011)
  • Author(s): 川島伸之
  • Organizer: 日本歯科大学エキスパートセミナー
  • Place of Presentation: 新潟
  • Invited
• [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
• [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
• [Presentation] 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、須田英明
  • 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
• [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: Athens, Greece
• [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: Athens, Greece
• [Presentation] Promotive effects of Sp7 on Dspp expression (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: Barcelona, Spain
• [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: Athens
• [Presentation] Shh Signaling is Related to BMP and Wnt Signaling in Ameloblast Diff exentiation (2010)
  • Author(s): S Takahashi, N Kawashima, K Katsube, T Sugiyama, H Sida
  • Organizer: 8th World Endodontic Congress
  • Place of Presentation: Athens
• [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: Athens
• [Presentation] Analysis of osteoblastic mesenchymal cell adhesion on laser-induced dentin modification (2010)
  • Author(s): G Bolortuya, A Ebihara, S Watanabe, T Anjo, C Kokuzawa, H Saegusa, N Kawashima, H Suda
  • Organizer: 8th World Endodontic Congress
  • Place of Presentation: Athens
• [Presentation] Promotive effects of Sp7 on Dspp expression (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: Barcelona
• [Presentation] Effects of MMP-3 on Inflammatory Mediator Synthesis from Macrophages (2010)
  • Author(s): K Takimoto, N Kawashima, M Nakashima, H Nakamura, Y Koizumi, H Suda
  • Organizer: 89th IADR General Session & Exhibition
  • Place of Presentation: Barcelona
• [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: Barcelona
• [Presentation] Expression of Vasoactive Intestinal Peptide Receptors in HERS Cells (2009)
  • Author(s): J Xu, N Kawashima, N Fujiwara, H Harada, H Suda
  • Organizer: 89th IADR General Session & Exhibition
  • Place of Presentation: Barcelona