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Study of periodontal tissue regeneration by mesenchymal stem cells with enhanced anti-inflammatory effects.

Research Project

Project/Area Number 25463053
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dental engineering/Regenerative dentistry
Research InstitutionIwate Medical University

Principal Investigator

Chosa Naoyuki  岩手医科大学, 歯学部, 講師 (80326694)

Co-Investigator(Renkei-kenkyūsha) Ishisaki Akira  岩手医科大学, 歯学部, 教授 (20356439)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
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: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords歯周組織再生 / 間葉系幹細胞 / 炎症性サイトカイン / アンタゴニスト / 細胞治療 / ケモカイン
Outline of Final Research Achievements

Mesenchymal stem cells (MSCs) are migrated into the inflammatory tissues by chemokines, such as SDF-1 and MCP-1, following which the effects as anti-inflammatory and tissue repair. In this study, we investigate the interaction with MSCs and periodontal ligament fibroblasts (PDL-Fs), and then examine the role of the MSCs in periodontitis accompanied by tissue disruption. Inflammatory cytokines such as IL-1β, IL-6, and TNF-α were promoted the expression of a chemokine, MCP-1, in the PDL-Fs. Expression of MSC marker such as Sca-1 and CD44 were enhanced in MSCs that are directly co-cultured with PDL-Fs. Importantly, in conjunction with suppression of a pro-inflammatory cytokine, IL-6, expression and promotion of anti-inflammatory cytokines, IL-10 and TGF-β, expression were observed. These results were suggested that anti-inflammatory effects of the MSCs is enhances, which interacts with the periodontal tissue cells by cell-cell adhesion in periodontitis.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (43 results)

All 2016 2015 2014 2013 Other

All Journal Article (16 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 16 results,  Acknowledgement Compliant: 8 results,  Open Access: 9 results) Presentation (26 results) (of which Invited: 1 results) Remarks (1 results)

  • [Journal Article] Establishment of mesenchymal stem cell lines derived from the bone marrow of GFP-transgenic mice exhibiting diversity in intracellular TGF-β and BMP signaling.2016

    • Author(s)
      Sawada, S., Chosa, N., Takizawa, N., Yokota, J., Igarashi, Y., Tomoda, K., Kondo, H., Yaegashi, T., and Ishisaki, A.
    • Journal Title

      Mol. Med. Rep.

      Volume: 13 Issue: 3 Pages: 2023-2031

    • DOI

      10.3892/mmr.2016.4794

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] VEGF-C and TGF-β reciprocally regulate mesenchymal stem cell commitment to differentiation into lymphatic endothelial or osteoblastic phenotypes.2016

    • Author(s)
      Igarashi Y, Chosa N, Sawada S, Kondo H, Yaegashi T, Ishisaki A.
    • Journal Title

      Int J Mol Med.

      Volume: 37(4) Issue: 4 Pages: 1005-1013

    • DOI

      10.3892/ijmm.2016.2502

    • NAID

      120006334508

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Zoledronic acid suppresses transforming growth factor-β (TGF-β)-induced fibrogenesis by human gingival fibroblasts possibly through down-regulation of TGF-β type I receptor expression2016

    • Author(s)
      Komatsu Y., Ibi M., Chosa N., Kyakumoto S., Kamo M., Shibata T., Sugiyama Y., Ishisaki A.
    • Journal Title

      International Journal of Molecular Medicine

      Volume: 37

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Recruitment of mesenchymal stem cells by stromal cell-derived factor 1α in pulp cells from deciduous teeth2015

    • Author(s)
      Akazawa Y., Hasegawa T., Yoshimura Y., Chosa N., Asakawa T., Ueda K., Sugimoto A., Kitamura T., Nakagawa H., Ishisaki A., Iwamoto T.
    • Journal Title

      International Journal of Molecular Medicine

      Volume: 36 Issue: 2 Pages: 442-448

    • DOI

      10.3892/ijmm.2015.2247

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Establishment of immortalized mesenchymal stem cells derived from the submandibular glands of tdTomato transgenic mice.2015

    • Author(s)
      Furukawa, S., Kuwajima, Y., Chosa, N., Satoh, K., Ohtsuka, M., Miura, H., Kimura, M., Inoko, H., Ishisaki, A., Fujimura, A., and Miura, H.
    • Journal Title

      Exp. Ther. Med.

      Volume: 10 Issue: 4 Pages: 1380-1386

    • DOI

      10.3892/etm.2015.2700

    • NAID

      120006334507

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of mesenchymal stem cell lines derived from the bone marrow of GFP-transgenic mice exhibiting diversity in intracellular TGF-β and BMP signaling2015

    • Author(s)
      Sawada S., Chosa N., Takizawa N., Yokota J., Igarashi Y., Tomoda K., Kondo H., Yaegashi T., Ishisaki A.
    • Journal Title

      Molecular Medicine Reports

      Volume: 12

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Re-examination of a α-chymotrypsin-solubilized laccase in the pupal cuticle of the silkworm, Bombyx mori: insights into the regulation system for laccase activation during the ecdysis process2014

    • Author(s)
      T. Asano, M. Taoka, Y. Yamauchi, R. C. Everroad, Y. Seto, T. Isobe, M. Kamo, N. Chosa
    • Journal Title

      Insect Biochemistry and Molecular Biology

      Volume: 55 Pages: 61-69

    • DOI

      10.1016/j.ibmb.2014.10.004

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The homeobox gene DLX4 promotes generation of human induced pluripotent stem cells2014

    • Author(s)
      Naritaka Tamaoki, Kazutoshi Takahashi, Hitomi Aoki, Kazuki Iida, Tomoko Kawaguchi, Daijirou Hatakeyama, Masatoshi Inden, Naoyuki Chosa, Akira Ishisaki, Takahiro Kunisada, Toshiyuki Shibata, Naoki Goshima, Shinya Yamanaka, and Ken-ichi Tezuka
    • Journal Title

      Scientific Reports

      Volume: なし Issue: 1 Pages: 7283-7283

    • DOI

      10.1038/srep07283

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Tracking GFP-labeled Transplanted Mouse MSC in Nude Mice Using in Vivo Fluorescence Imaging2014

    • Author(s)
      Taira M., Hatakeyama W., Yokota J., Chosa N., Ishisaki A., Takafuji K., Kihara H., Kondo H., Hattori M.
    • Journal Title

      Nano Biomedicine

      Volume: 6 Issue: 2 Pages: 73-77

    • DOI

      10.11344/nano.6.73

    • NAID

      130005130560

    • ISSN
      1883-5198, 2185-4734
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 間葉系幹細胞のstemnessを維持するシグナル伝達経路2014

    • Author(s)
      帖佐直幸, 菊池-青松恵美子, 西平宗功, 横田潤, 高橋典子, 近藤尚知, 杉山芳樹, 三浦廣行, 石崎明.
    • Journal Title

      岩手医科大学歯学雑誌

      Volume: 39 Pages: 56-65

    • NAID

      110009857549

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] PDGF-induced PI3K-mediated signal enhances TGF-βinduced osteogenic differentiation of human mesenchymal stem cells in the TGF-β-activated MEK-dependent manner2014

    • Author(s)
      Jun Yokota, Naoyuki Chosa, Shunsuke Sawada, Naoto Okubo, Noriko Takahashi, Tomokazu Hasegawa, Hisatomo Kondo, Akira Ishisaki
    • Journal Title

      International Journal of Molecular Medicine

      Volume: 33 Issue: 3 Pages: 534-542

    • DOI

      10.3892/ijmm.2013.1606

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell-cell adhesion through N-cadherin enhances VCAM-1 expression via PDGFRβ in a ligand-independent manner in mesenchymal stem cells.2014

    • Author(s)
      Aomatsu, E., Chosa, N., Nishihira, S., Sugiyama, Y., Miura, H., and Ishisaki, A.
    • Journal Title

      International Journal of Molecular Medicine

      Volume: 33 Issue: 3 Pages: 565-572

    • DOI

      10.3892/ijmm.2013.1607

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of tongue cleaning on bacterial flora in tongue coating and dental plaque: A crossover study.2014

    • Author(s)
      Matsui, M., Chosa, N., Shimoyama, Y., Minami, K., Kimura, S., Kishi, M.
    • Journal Title

      BMC Oral Health

      Volume: 14 Issue: 1 Pages: 4-4

    • DOI

      10.1186/1472-6831-14-4

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel SCRG1/BST1 axis regulates self-renewal, migration, and osteogenic differentiation potential in mesenchymal stem cells.2014

    • Author(s)
      Aomatsu, E., Takahashi, N., Sawada, S., Okubo, N., Hasegawa, T., Taira, M., Miura, H., Ishisaki, A., and Chosa, N.
    • Journal Title

      Sci. Rep.

      Volume: 4 Issue: 1 Pages: 3652-3652

    • DOI

      10.1038/srep03652

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] EGF positively regulates the proliferation and migration, and negatively regulates the myofibroblast differentiation of periodontal ligament-derived endothelial progenitor cells through MEK/ERK- and JNK-dependent signals.2013

    • Author(s)
      Kimura, H., Okubo, N., Chosa, N., Kyakumoto, S., Kamo, M., Miura, H. and Ishisaki, A
    • Journal Title

      Cell. Physiol. Biochem.

      Volume: 32 Issue: 4 Pages: 899-914

    • DOI

      10.1159/000354493

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of apatite particle size contained in two apatite/collagen composites on osteogenic differentiation profile in osteoblastic cells.2013

    • Author(s)
      Hatakeyama W., Taira M., Chosa N., Kihara H., Ishisaki A., Kondo H.
    • Journal Title

      International Journal of Molecular Medicine

      Volume: 32 Issue: 6 Pages: 1255-1261

    • DOI

      10.3892/ijmm.2013.1516

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 間葉系幹細胞由来ペプチドSCRG1はRANKL誘導性破骨細胞分化を抑制する2015

    • Author(s)
      菊池恵美子
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] 成長因子が歯周靭帯由来血管内皮前駆細胞(EPC)の分化に与える影響について2015

    • Author(s)
      木村仁迪
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] 顎関節組織由来細胞におけるTGF-β誘導性抗炎症性作用発現の調節機構を明らかにする研究2015

    • Author(s)
      横田聖司
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] 歯根膜線維芽細胞との細胞間相互作用は間葉系幹細胞の抗炎症作用を増強する2015

    • Author(s)
      鈴木啓太
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] TGF-β1刺激によりWnt5bを介して発現増大するMMP-10はヒト扁平上皮癌細胞株HSC-4の浸潤能に関与する2015

    • Author(s)
      樋野雅文
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Zolerdronic acidはTGF-β タイプ Ι レセプターの発現を低下させることにより筋線維芽細胞への分化を阻害する2015

    • Author(s)
      小松ゆう子
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] TGF-β 刺激により顎関節組織由来細胞が示す病的機能変化の調節機構を明らかにする研究2015

    • Author(s)
      横田聖司
    • Organizer
      第57回歯科基礎医学会学術大会・総会
    • Place of Presentation
      新潟
    • Year and Date
      2015-09-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] マウス骨髄由来間葉系幹細胞は共培養下で未分化単球/マクロファージ系細胞をCD206 陽性の免疫抑制性(M2)マクロ ファージに分化誘導する2015

    • Author(s)
      客本斉子
    • Organizer
      第57回歯科基礎医学会学術大会・総会
    • Place of Presentation
      新潟
    • Year and Date
      2015-09-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] VEGF-Cは骨髄由来間葉系幹細胞の増殖や遊走を促進する2015

    • Author(s)
      五十嵐靖之
    • Organizer
      第57回歯科基礎医学会学術大会・総会
    • Place of Presentation
      新潟
    • Year and Date
      2015-09-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] Zolerdronic acid は TGF-β 刺激による歯肉線維芽細胞の受容体発現に伴うSmad経路を介した線維化機構を阻害する2015

    • Author(s)
      小松ゆう子
    • Organizer
      第57回歯科基礎医学会学術大会・総会
    • Place of Presentation
      新潟
    • Year and Date
      2015-09-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] 異なる間葉系幹細胞の協調的作用を利用した歯周組織再生2015

    • Author(s)
      帖佐直幸
    • Organizer
      第57回歯科基礎医学会学術大会・総会
    • Place of Presentation
      新潟
    • Year and Date
      2015-09-11
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] ヒトDown症候群歯根膜由来細胞におけるSDF‐1α発現解析2015

    • Author(s)
      浅川剛吉
    • Organizer
      第53回日本小児歯科学会大会
    • Place of Presentation
      広島
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 乳歯歯根膜由来細胞のSDF‐1αを介した歯周組織恒常性に関わる細胞間相互作用2015

    • Author(s)
      長谷川智一
    • Organizer
      第53回日本小児歯科学会大会
    • Place of Presentation
      広島
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] TGF-β1はヒト扁平上皮癌細胞株HSC-4細胞においてMMP-10を介した浸潤能を誘導する2014

    • Author(s)
      樋野雅文
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都国際会館
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Research-status Report
  • [Presentation] SCRG1は受容体BST1を介して間葉系幹細胞のstemness維持を調節する2014

    • Author(s)
      菊池-青松恵美子
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都国際会館
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Research-status Report
  • [Presentation] VEGFはTGF-βによって誘導される間葉系幹細胞の骨分化を増強する2014

    • Author(s)
      横田潤
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都国際会館
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Research-status Report
  • [Presentation] 口腔軟組織におけるBisphosphonate製剤の作用に着目したBRONJ発症機序の探求2014

    • Author(s)
      小松ゆう子
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都国際会館
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Research-status Report
  • [Presentation] tdTomato遺伝子導入マウス唾液腺由来間葉系幹細胞株の樹立2014

    • Author(s)
      古川真司
    • Organizer
      第56回歯科基礎医学会学術大会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] マウス骨髄由来異種細胞共培養系の確立2014

    • Author(s)
      滝沢尚希
    • Organizer
      第56回歯科基礎医学会学術大会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] ファイブロサイトに注目した顎関節領域疾患発症機構の解明2014

    • Author(s)
      衣斐美歩
    • Organizer
      第56回歯科基礎医学会学術大会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] ヒト口腔扁平上皮癌細胞HSC-4におけるTGF-β1誘導性上皮間葉転換とintegrin α3β1依存的な細胞遊走能はSlugを介する2013

    • Author(s)
      加茂政晴 齋藤大嗣 客本斉子 衣斐美歩 帖佐直幸 石崎明
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] EGFが歯周靭帯由来血管内皮前駆細胞の増殖と筋線維芽細胞分化に与える影響について2013

    • Author(s)
      木村仁迪 大久保直登 帖佐直幸 衣斐美歩 客本斉子 加茂政晴 金野吉晃  三浦廣行 石崎明
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] サイトカイン様ペプチドSCRG1は間葉系幹細胞の骨ならびに脂肪分化を抑制する2013

    • Author(s)
      青松恵美子 帖佐直幸 大久保直登 衣斐美歩 高橋典子 客本斉子 加茂政晴  長谷川智一 佐藤和朗 三浦廣行 石崎明
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] 間葉系幹細胞が分泌するSCRG1は骨分化を抑制する2013

    • Author(s)
      青松恵美子 帖佐直幸 衣斐美歩 客本斉子 加茂政晴 長谷川智一 佐藤和朗  三浦廣行 石崎明
    • Organizer
      第55回歯科基礎医学会学術大会
    • Place of Presentation
      岡山
    • Related Report
      2013 Research-status Report
  • [Presentation] 複数サイトカインによる同時刺激は間葉系幹細胞の骨分化誘導性を促進する2013

    • Author(s)
      横田潤 帖佐直幸 高橋典子 衣斐美歩 客本斉子 加茂政晴 長谷川智一  近藤尚知 石崎明
    • Organizer
      第55回歯科基礎医学会学術大会
    • Place of Presentation
      岡山
    • Related Report
      2013 Research-status Report
  • [Presentation] EGFによるPDL由来EPCの増殖、分化制御2013

    • Author(s)
      木村仁迪 大久保直登 帖佐直幸 衣斐美歩 客本斉子 加茂政晴 金野吉晃  三浦廣行 石崎明
    • Organizer
      第55回歯科基礎医学会学術大会
    • Place of Presentation
      岡山
    • Related Report
      2013 Research-status Report
  • [Remarks] 研究内容ならびに研究成果の公表

    • URL

      http://cellbiosignal.jp/

    • Related Report
      2014 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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