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Osteogenic and angiogenic activity of hypertrophic chondrocytes and its clinical application

Research Project

Project/Area Number 15592097
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionThe University of Tokyo

Principal Investigator

MORI Yoshiyuki  The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (70251296)

Co-Investigator(Kenkyū-buntansha) TAKATO Tsuyoshi  The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 教授 (90171454)
TEI Yuichi  The University of Tokyo, Graduate School of Medical Science, Associate Professor, 大学院・医学系研究科, 助教授 (30345053)
OGIHARA Yuji  The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (20345226)
HIKIJI Hisako  The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (50292876)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordscartilage / hypertrophy / angiogenesis / osteogenesis
Research Abstract

1.Establishment of the method to differentiate isolated mesenchymal stromal cells into chondrocytes
We isolated mesenchymal stromal cells from a transgenic mouse line which expressed green fluorescent protein (GFP) under the control of the osteoblast-specific type I collagen promoter. Using these cells as a detector, we screened combinations of various chondrogenic factors for the optimal signaling. As a result, we identified the combination of Sox5, Sox6, and Sox9 was the most efficient and cell-type independent signaling unit. Treatment with the combination induced mRNA expression of cartilage marker genes, such as type II collagen, type IX collagen, and type XI collagen, aggrecan, and cbondromodulin-1. The treatment also induced expression of cartilage-specific matrix detected by immunohistuchemistry for type II Collagen and toluidine Blue stainin
2.Establishment of the method to induce hypertcophic differentiation of chondrocytes
We treated chondrocyte-differentiated mesenchymal stromal cells, a undifferentiated mesenchymal cell line C3H10T1/2, and primary rib chondrocytes with various signaling molecules to find out that the canonical Wnt signaling pathway and Runx2 signaling pathway promoted hypertrophic differentiation detected by real-time RT-PCRT for type X collagen. In contrast, the loss of the gene endoding a stimulatory G protein, a putative inhibitory factor for hypertrophy, resulted in accelerated hypertrophy of chondrocytes in vivo.
3.Induction of angiogenesis and osteogenesis by mineralized hypertrophic chondrocytes
We isolated chondrocytes from rabbit ribs and treated them with the canonical Wnt signal in osteogenic medium to induce hypertrophic differentiation and calcification. We formed pellets from these cells and transplanted subcutaneously into the back of rabbits. Angiogenesis into the pellets was observed at 2 weeks after the surgery. At 4 weeks after the surgery, osteogenesis occurred with bone marrow space.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (27 results)

All 2004 2003 Other

All Journal Article (18 results) Book (5 results) Publications (4 results)

  • [Journal Article] Stimulatory G protein (Gs) directly regulates hypertrophic differentiation of growth plate cartilage in vivo.2004

    • Author(s)
      Bastepe M, Weinstein LS, Ogata N, Kawaguchi H, Juppner H, Kronenberg HM, Chung U.
    • Journal Title

      Proc Nat Acad Sci USA 101

      Pages: 14794-14799

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Essential role of hypertrophic chondrocytes in endochondral bone development.2004

    • Author(s)
      Chung U.
    • Journal Title

      Endocrine Journal 51

      Pages: 19-24

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] 舌痛症2004

    • Author(s)
      森 良之
    • Journal Title

      ドクターサロン 48,6

      Pages: 25-28

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 舌痛症2004

    • Author(s)
      森 良之
    • Journal Title

      総合臨床 12

      Pages: 3141-3142

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] 骨延長に関連した基礎的研究2004

    • Author(s)
      森 良之, 西條英人, 江口智明, 高戸 毅
    • Journal Title

      口唇口蓋裂における基礎研究と予防の現状

      Pages: 97-107

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Stimulatory G protein (Gs)directly regulates hypertrophic differentiation of growth plate cartilage in vivo.2004

    • Author(s)
      Bastepe M, Weinstein LS, Ogata N, Kawaguchi H, Juppn
    • Journal Title

      Proc Nat Acad Sci USA 101

      Pages: 14794-14799

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 舌痛症2004

    • Author(s)
      森 良之
    • Journal Title

      ドクターサロン 48, 6

      Pages: 25-28

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 骨延長に関連した基盤的研究2004

    • Author(s)
      森 良之, 西條 英人, 江口 智明, 高戸 毅
    • Journal Title

      口唇口蓋裂における基盤研究と予防の現状

      Pages: 97-107

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Secondary correction of wide nasal root of bilateral cleft-associated nasal deformity in Orientals.2003

    • Author(s)
      Omori M, Takato T, Eguchi T, Mori Y.Tomizuka K.
    • Journal Title

      Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery 37

      Pages: 177-181

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Attempt for prevention of Cleft Lip and Palate in Japan.2003

    • Author(s)
      Natsume N, Kawai T, Yoshida Tomoda Y, Sakai E, Sumiyoshi Y, Hirahara F, Mori Y.
    • Journal Title

      Dentistry in Japan 39

      Pages: 194-198

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 歯科用キシロカイン^<【○!R】>中に含まれるピロ亜硫酸ナトリウムによるアナフィラキシーショックの1例2003

    • Author(s)
      西條英人, 西川久美子, 森 良之, 小泉敏之, 坂田康彰, 高戸 毅
    • Journal Title

      日本口腔外科学会雑誌 49(3)

      Pages: 237-240

    • NAID

      10012628981

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 自己フィブリン糊の応用-自己血輸血実施上のマネジメント2003

    • Author(s)
      森 良之, 高戸 毅
    • Journal Title

      口腔外科領域の自己血輸血実施上の留意点-総貯血量に基づく採血計画

      Pages: 79-83

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 第II編3.4.治療計画の説明2003

    • Author(s)
      森 良之, 高戸 毅
    • Journal Title

      歯科医療事故予防学

      Pages: 133-135

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Secondary correction of wide nasal root of bilateral cleft-associated nasal deformity in Orientals.2003

    • Author(s)
      Omori M., Takato T., Eguchi T., Mori Y., Tomizuka K.
    • Journal Title

      Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery 37

      Pages: 177-181

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Attempt for prevention of Cleft Lip and Palate in Japan.2003

    • Author(s)
      Natsume N., Kawai T., Yoshida W., Tomoda Y., Sakai E., Sumiyoshi Y., Hirahara F., Kohama G., Noguchi M., Endo T., Sugiyama Y., Fukushima A., Echigo S., Saito C., Uchiyama T., Tanabe K., Yoshimasu H., Enomoto S., Omura K., Kubota T., Takato T., Kozuma S., Kurita K., Suzumori K., Matsuya T., Kogo M,, Sakuda M., Mori Y., Murata Y., Yoshimura Y., Muyazaki K., Ohishi M., Tsukimori K., Katsuki T., Yamagisawa S., Miyakawa I., Shiba R., Ikenoue T., Sugihara K., Mimura T., Ikuta Y., Sunakawa H., Kanazawa K., Shinozato K.
    • Journal Title

      Dentistry in Japan 39

      Pages: 194-198

    • NAID

      10016197137

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Shikayohkishirokainchunifukumarerupiroaryusannatoriumniyoruanafirakishisyokkunoichirei.2003

    • Author(s)
      Saijyo H., Nishikawa K., Mori Y., Koizumi T., Sakata Y., Takato T.
    • Journal Title

      Japanese Journal of oral & Maxillofacial surgery 9(3)

      Pages: 237-240

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Total upper lip reconstruction after surgical resection of malignant melanoma.

    • Author(s)
      Eguchi T, Nakatsuka T, Mori Y.Takato T.
    • Journal Title

      Scand.J.Plast.Reconstr.Surg.Hand Surg. (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Total upper lip reconstruction after surgical resection of malignant melanoma.

    • Author(s)
      Eguchi T., Nakatsuka T., Mori Y., Takato T.
    • Journal Title

      Scand.J.Plast.Reconstr.Surg.Hand Surg. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Dr.salon 「Zettusyo」2004

    • Author(s)
      Mori Y
    • Publisher
      Kyobundo.Co.Ltd, Tokyo
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] General medical sciense 「Zettusyo」2004

    • Author(s)
      Mori Y
    • Publisher
      Nagai Shoten Co., Ltd., Osaka
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] koushinkougairetsuniokerukisokenkyutoyobohunogenjyoh 「kotsuentyohnikanrenshitakisotekikenkyu」2004

    • Author(s)
      Mori Y., Saijyo H., Eguchi T., Takato T.
    • Publisher
      Neo Medic cc, Ltd, nagoya
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Koukuugekaryoikinojikoyuketsujisshijyohnoryuiten-souchoketuryohnimotodukusaiketsukeikaku, jikofiburinkonoouyou-jikoyuketsujisshijyohnomanejimento2003

    • Author(s)
      Mori Y., Takato T.
    • Publisher
      Iyaku (Medicine and Drug) Journal Co., Ltd
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] A study of the dentistry medical treatment accident prevention 「the explanation of 第II編 3.4.treatment plan」2003

    • Author(s)
      Mori Y., Takato T.
    • Publisher
      Ishiyaku Publishers, Inc.
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Omori M., Takato T., Eguchi T., Mori Y., Tomizuka K.: "Secondary correction of wide nasal root of bilateral cleft-associated nasal deformity in Orientals."Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. 37. 177-181 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Chung U: "Essential role of hypertrophic chondrocytes in endochondral bone development"Endocrine Journal. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Koizumi T., Hikiji H., Shin.WS., Takato T., Fukuda S.他4名: "Cell Dentistry and growth-dependent down-regulation of both intracellular calcium responses to agonist stimuli and expression of smooth-surfaced endoplasmic reticulum in MC3T3-E1 osteoblast-like cells"J Biol Chem. 278. 6433-6439 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 西條英人, 江口智明, 引地尚子, 高戸 毅, 中塚貴志: "顎矯正力を応用した家兎下顎骨延長法に関する実験的研究"日本形成外科学会会誌. 23. 574-581 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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