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Elucidation of mechanisms underlying regulation of proliferation and differentiation of mesenchymal stem cells derived from periodontal ligament

Research Project

Project/Area Number 20592169
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionIwate Medical University

Principal Investigator

ISHISAKI Akira  Iwate Medical University, 歯学部, 教授 (20356439)

Co-Investigator(Kenkyū-buntansha) 飯塚 正  北海道大学, 大学院・歯学研究科, 准教授 (80168062)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords幹細胞 / 歯根膜 / 再生医療 / 再生医学 / 間葉系幹細胞 / 転写因子 / 歯学 / 細胞・組織 / 血管内皮細胞 / 骨芽細胞 / 細胞分化
Research Abstract

To elucidate molecular mechanisms underlying the regulation of proliferation and differentiation of mesenchymal stem cells (MSCs) derived from periodontal ligament (PDL), we established two types of single cell-derived cultures (SCDCs) of rat ligament cells, one of which named as SCDC2 retained the ability of self-renewal and multipotency and another of which named as SCDC1 did not. Then, we comprehensively compared the genes expression status and phosphorylation status of intracellular molecules between SCDC1 and SCDC2. We found that among 54,000 target genes, around 600 genes were identified as differentially expressed genes between the two types of cells. In particular, we found that some transcription factors, which were previously reported as proliferation and differentiation regulators of several kinds of stem cells, were highly expressed in the SCDC2 cells. Moreover, we found that the FGF-induced- and TGF--induced-intracellular signaling played important roles on the regulation of proliferation and differentiation of the MSCs. Thus, we successfully elucidated the molecular mechanisms underlying the regulation of proliferation and differentiation of MSCs derived from PDL.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (46 results)

All 2011 2010 2009 2008 Other

All Journal Article (22 results) (of which Peer Reviewed: 22 results) Presentation (24 results)

  • [Journal Article] Plasminogen/plasmin modulates bone metabolism by regulating the osteoblast and osteoclast function.2011

    • Author(s)
      Kanno Y, Ishisaki A, Kawashita E, Chosa N, Nakajima K, Nishihara T, Toyoshima K, Okada K, Ueshima S, Matsushita K, Matsuo O, Matsuno H.
    • Journal Title

      J Biol Chem 286

      Pages: 8952-8960

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] High-cell density-induced VCAM1 expression inhibits the migratory ability of mesenchymal stem cells.2011

    • Author(s)
      Nishihira S, Okubo N, Takahashi N, Ishisaki A, Sugiyama Y, Chosa N
    • Journal Title

      Cell Biol Int 35

      Pages: 475-481

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bovine milk lactoferrin induces synthesis of the angiogenic factors VEGF and FGF2 in osteoblasts via the p44/p42 MAP kinase pathway2011

    • Author(s)
      Kei-ichi Nakajima
    • Journal Title

      Biometals

      Volume: (Epub ahead of Print)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Plasminogen/plasmin modulates bone metabolism by regulating the osteoblast and osteoclast function2011

    • Author(s)
      Yosuke Kanno
    • Journal Title

      Journal of Biological Chemistry

      Volume: 286 Pages: 8952-8960

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High-cell density-induced VCAM1 expression inhibits the migratory ability of mesenchymal stem cells2011

    • Author(s)
      Soko Nishihira
    • Journal Title

      Cell Biology International

      Volume: 35 Pages: 475-481

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of immortalized human periodontal ligament cells derived from deciduous teeth.2010

    • Author(s)
      Hasegawa T,Chosa N, Asakawa T, Yoshimura Y, Ishisaki A, Tanaka M.
    • Journal Title

      Int J Mol Med 26

      Pages: 701-705

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effect of fibroblast growth factor-2 on periodontal ligament cells derived from human deciduous teeth in vitro.2010

    • Author(s)
      Hasegawa T, Chosa N, Asakawa T, Yoshimura Y, Asakawa A, Ishisaki A, Tanaka M.
    • Journal Title

      Exp Ther Med 3

      Pages: 337-341

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effect of fibroblast growth factor-2 on dental pulp cells derived from human deciduous teeth in vitro.2010

    • Author(s)
      Hasegawa T, Chosa N, Asakawa T, Yoshimura Y, Asakawa A, Ishisaki A, Tanaka M.
    • Journal Title

      Exp Ther Med 1

      Pages: 477-480

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Vascular cell-like potential of undifferentiated ligament fibroblasts to construct vascular cell-specific marker-positive blood vessel structures in a PI3K-activation-dependent manner.2010

    • Author(s)
      Okubo N, Ishisaki A, Iizuka T, Tamura M, Kitagawa Y.
    • Journal Title

      J Vasc Res 47

      Pages: 369-383

    • NAID

      120002400574

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 線維芽細胞増殖因子(FGF-1)によるラット歯周靭帯由来未分化間葉系細胞様細胞の増殖促進効果発現メカニズム2010

    • Author(s)
      高橋美香子, 大久保直登, 帖佐直幸, 高橋典子, 加茂政晴, 水城春美, 石崎明, 客本斉子
    • Journal Title

      口腔組織培養学会誌 20

      Pages: 23-24

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of immortalized human periodontal ligament cells derived from deciduous teeth2010

    • Author(s)
      Tomokazu Hasegawa
    • Journal Title

      International Journal of Molecular Medicine

      Volume: 26 Pages: 701-705

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of fibroblast growth factor-2 on dental pulp cells derived from human deciduous teeth in vitro2010

    • Author(s)
      Tomokazu Hasegawa
    • Journal Title

      Tomokazu Hasegawa

      Volume: 1 Pages: 477-480

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 線維芽細胞増殖因子(FGF-1)によるラット歯周靭帯由来未分化間葉系細胞様細胞の増殖促進効果発現メカニズム2010

    • Author(s)
      高橋美香子
    • Journal Title

      口腔組織培養学会誌

      Volume: 20 Pages: 358-363

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of fibroblast growth factor-2 on periodontal ligament cells derived from human deciduous teeth in vitro2010

    • Author(s)
      Tomokazu Hasegawa
    • Journal Title

      Exp.Ther.Med. 3

      Pages: 337-341

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synergistic effect of dexamethasone and prolactin on VEGF expression bovine mammary epithelial cells via p44/p42 MAP kinase.2009

    • Author(s)
      Nakajima K, Nakamura M, Ishisaki A, Kozakai T.
    • Journal Title

      Asian-Austral.J.Animal Sci. 22

      Pages: 788-795

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Multipotency of clonal cells derived from swine periodontal ligament and differential regulation by fibroblast growth factor and bone morphogenetic protein.2009

    • Author(s)
      Shirai K, Ishisaki A, Kaku T, Tamura M, Furuichi Y.
    • Journal Title

      J Periodontal Res 44

      Pages: 238-247

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 骨における血管新生と線溶系2009

    • Author(s)
      帖佐直幸、石崎明
    • Journal Title

      血栓止血学会誌 20

      Pages: 12-17

    • NAID

      10026117053

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synergistic effect of dexamethasone and prolactin on VEGF expression bovine mammary epithelial cells via p44/p42 MAP kinase2009

    • Author(s)
      Kei-Ichi Nakajima
    • Journal Title

      Asian Austral.J.Anim. 22

      Pages: 788-795

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 歯根膜由来幹細胞様細胞による3次元培養下における血管内皮細胞マーカー陽性血管様構造の形成2009

    • Author(s)
      大久保直登
    • Journal Title

      口腔組織培養学会誌 19

      Pages: 29-30

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multipotency of clonal cells derived from swine periodontal ligament and differential regulation by fibroblast growth factor and bone morphogenetic protein.2009

    • Author(s)
      Kaname Shirai
    • Journal Title

      J Periodontal Res 44

      Pages: 238-247

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 骨における血管新生と線溶系2009

    • Author(s)
      帖佐直幸
    • Journal Title

      血栓止血誌 20

      Pages: 12-17

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bovine milk lactoferrin induces synthesis of the angiogenic factors VEGF and FGF2 in osteoblasts via the p44/p42 MAP kinase pathway.

    • Author(s)
      Nakajima K, Kanno Y, Nakamura M, Gao X-D, Kawamura A, Itoh F, Ishisaki A
    • Journal Title

      Biometals in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] 未分化間葉系細胞の増殖・分化制御メカニズムの解明-歯周靱帯再生医療の実現を目指して-2011

    • Author(s)
      石崎明
    • Organizer
      口腔先端応用医科学研究会第3回学術会議
    • Place of Presentation
      東京医科歯科大学(東京)
    • Year and Date
      2011-01-22
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] Plasminogen/Plasminの骨芽細胞及び破骨細胞機能調節による骨代謝制御2010

    • Author(s)
      菅野陽介
    • Organizer
      第33回日本分子生物学会年会第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸ポートアイランド(神戸)
    • Year and Date
      2010-12-10
    • Related Report
      2010 Final Research Report
  • [Presentation] Plasminogen/Plasminの骨芽細胞及び破骨細胞機能調節による骨代謝制御2010

    • Author(s)
      菅野陽介
    • Organizer
      第33回日本分子生物学会年会第83回日本生化学会大会合同大会
    • Place of Presentation
      ポートアイランド(神戸)
    • Year and Date
      2010-12-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] 線維芽細胞増殖因子(FGF-1)によるラット歯周靭帯由来未分化間葉系細胞様細胞の増殖促進効果発現メカニズム2010

    • Author(s)
      高橋美香子
    • Organizer
      第47回日本口腔組織培養学会学術大会
    • Place of Presentation
      高知県教育会館(高知)
    • Year and Date
      2010-11-13
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] ヒト乳歯歯根膜由来細胞におけるSDF-1の発現調節機構2010

    • Author(s)
      長谷川智一
    • Organizer
      第52回歯科基礎医学会学術大会
    • Place of Presentation
      タワーホール船堀(東京)
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] システインリッチペプチドSCRG1は間葉系幹細胞の移動能を促進する2010

    • Author(s)
      帖佐直幸
    • Place of Presentation
      タワーホール船堀(東京)
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] PDGF受容体を介したVCAM1の発現は間葉系幹細胞の遊走を制御する2010

    • Author(s)
      西平宗功
    • Place of Presentation
      タワーホール船堀(東京)
    • Year and Date
      2010-09-21
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] ラット歯根膜由来未分化間葉系細胞による血管様構造物の形成2010

    • Author(s)
      大久保直登
    • Organizer
      岩手医科大学歯学会第70回大会
    • Place of Presentation
      岩手医科大学(盛岡)
    • Year and Date
      2010-07-03
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] ヒト扁平上皮癌細胞におけるガレクチン-1とEGFRの相互作用によるアノイキス抑制作用2009

    • Author(s)
      加茂政晴
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2009-12-10
    • Related Report
      2010 Final Research Report
  • [Presentation] 歯根膜由来幹細胞様細胞による3次元培養下における血管内皮細胞マーカー陽性血管様構造の形成2009

    • Author(s)
      大久保直登
    • Place of Presentation
      昭和大学(東京)
    • Year and Date
      2009-12-05
    • Related Report
      2010 Final Research Report
  • [Presentation] 歯根膜由来幹細胞様細胞による3次元培養下における血管内皮細胞マーカー陽性血管様構造の形成2009

    • Author(s)
      大久保直登
    • Organizer
      第46回日本口腔組織培養学会学術大会・総会
    • Place of Presentation
      東京
    • Year and Date
      2009-12-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] ラット歯根膜由来間葉系幹細胞によるPI3K/Akt依存的なTie-2陽性血管構造の形成2009

    • Author(s)
      大久保直登
    • Organizer
      再生補綴医学研究会第2回学術会議
    • Place of Presentation
      ルブラ王山(名古屋)
    • Year and Date
      2009-11-27
    • Related Report
      2010 Final Research Report
  • [Presentation] 間葉系幹細胞におけるPDGFレセプターを介したVCAM1の発現解析2009

    • Author(s)
      西平宗功
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド(神戸)
    • Year and Date
      2009-10-23
    • Related Report
      2010 Final Research Report
  • [Presentation] 歯根膜由来幹細胞による血管内皮細胞マーカー陽性血管構造の形成2009

    • Author(s)
      大久保直登
    • Organizer
      第51回歯科基礎医学会学術大会
    • Place of Presentation
      朱鷺メッセ(新潟)
    • Year and Date
      2009-09-10
    • Related Report
      2010 Final Research Report
  • [Presentation] 歯根膜由来幹細胞による血管内皮細胞マーカー陽性血管構造の形成2009

    • Author(s)
      大久保直登
    • Organizer
      第18回硬組織再生生物学会
    • Place of Presentation
      札幌コンベンションセンター(札幌)
    • Year and Date
      2009-09-05
    • Related Report
      2010 Final Research Report
  • [Presentation] FGFとTGF-βスーパーファミリーの相互作用による未分化間葉系幹細胞の細胞増殖・分化制御機構の解明2009

    • Author(s)
      石崎明
    • Organizer
      第7回口腔医科学フロンティア学術集会
    • Place of Presentation
      徳島大学(徳島)
    • Year and Date
      2009-03-07
    • Related Report
      2010 Final Research Report
  • [Presentation] FGFとTGF-βスーパーファミリーの相互作用による未分化間葉系幹細胞の細胞増殖・分化制御機構の解明2009

    • Author(s)
      石崎 明
    • Organizer
      第7回口腔医科学フロンティア学術集会
    • Place of Presentation
      徳島大学
    • Year and Date
      2009-03-07
    • Related Report
      2008 Annual Research Report
  • [Presentation] 間葉系幹細胞が分泌するシステインリッチペプチドSCRG1の機能解析2008

    • Author(s)
      高橋典子
    • Organizer
      第31回日本分子生物学会年会第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸ポートアイランド(神戸)
    • Year and Date
      2008-12-11
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒト口腔扁平上皮癌細胞におけるガレクチン-1のアノイキス抑制機構の解析2008

    • Author(s)
      加茂政晴
    • Organizer
      第31回日本分子生物学会年会第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸ポートアイランド(神戸)
    • Year and Date
      2008-12-09
    • Related Report
      2010 Final Research Report
  • [Presentation] Fas誘導アポトーシス経路におけるHSP90とFLIPの役割2008

    • Author(s)
      客本斉子
    • Organizer
      第31回日本分子生物学会年会第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸ポートアイランド(神戸)
    • Year and Date
      2008-12-09
    • Related Report
      2010 Final Research Report
  • [Presentation] パネルディスカッション-そして未来へその2予研から大学へ歯科研究の現状とこれから2008

    • Author(s)
      石崎明
    • Organizer
      予研歯科衛生部設立50周年記念講演
    • Place of Presentation
      目黒雅叙園(東京)
    • Year and Date
      2008-11-22
    • Related Report
      2010 Final Research Report
  • [Presentation] Mycoplasma salivariumにおけるヌクレアーゼの存在とその特性2008

    • Author(s)
      小川恵子
    • Organizer
      第45回日本口腔組織培養学会
    • Place of Presentation
      松本歯科大学(塩尻)
    • Year and Date
      2008-11-15
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒト歯根膜細胞群の多様性に関する解析2008

    • Author(s)
      日高竜宏
    • Organizer
      第51回秋季日本歯周病学会学術大会
    • Place of Presentation
      四日市市分化会館(四日市市)
    • Year and Date
      2008-10-19
    • Related Report
      2010 Final Research Report
  • [Presentation] The effects of butyrate, EGF, FGF-1 and TGF-beta on the expression of sodium/monocarboxylate transporter-1 (SMCT-1).2008

    • Author(s)
      Takaharu Kozakai
    • Organizer
      The 28^<th> Sapporo Cancer Seminar
    • Place of Presentation
      Sapporo, Japan
    • Year and Date
      2008-06-26
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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