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Development of drugs for osteoporosis using transgenic mice

Research Project

Project/Area Number 07557096
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Orthopaedic surgery
Research InstitutionTokyo Medical and Dental University

Principal Investigator

NODA Masaki  Tokyo Medical and Dental University, Medical Research Institute, professor, 難治疾患研究所, 教授 (50231725)

Co-Investigator(Kenkyū-buntansha) TAMURA Masato  Kagoshima Univ., School of Dent., Assistant Professor, 歯学部, 助手 (30236757)
NIFUJI Akira  Tokyo Medical and Dental University, Medical Research institute, Lecturer, 難治疾患研究所, 講師 (00240747)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥20,300,000 (Direct Cost: ¥20,300,000)
Fiscal Year 1997: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1996: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1995: ¥10,900,000 (Direct Cost: ¥10,900,000)
Keywordsbone / ligament / osteoporosis / osteoblast / transcription / promoter / type I collagen / transgenic animal / 遺伝子発現 / 靭帯 / BMP / 骨形成 / スクリーニング系 / 移植 / ベータガラクトシダーゼ / 薬剤スクリーニング / 転写因子 / トランスジェニックマウス / ベータガラトクシダーゼ / osteoblast / transcription / osteoclast / cytokine / osteoporosis / differention
Research Abstract

We generated chloromphenicol acetyl transferase reporter construct using 1kb promoter region of rat osteocalcin gene and analyzed the transcriptional activity. Collagen (type I) is a major bone protein which comprises about 90% of the matrix activity in vivo. Betagalactosidase reporter construct was used for this collagen promoter study. Both osteocalcin and collagen promoter activity was confirmed in in vivo experiments. Furthemore, bone-forming agents, such as TGFbeta and BMP were found to be able to stimulate production of collagen and activation of the promoters. The transgenic animals containing collagen promoter fragment are useful for studying bone-related agents.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (42 results)

All Other

All Publications (42 results)

  • [Publications] T.Yamashita, M.Noda et al.: "Elongation of the epiphyseal trabecular bone associated with precoclous aging in transgenic mice carrying an inserfional mutaiton in Klotho gene locus." Journal of Bone and Mineral Research. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Tsuji, M.Noda et al.: "Perturbation of BMP signaling in somitogenesis resulted in vertebral and rib molformation in the axial skeletal formation." Bone. 22・2. 87-92 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Murakami, M.Noda et al.: "Expression of Indiana Hedgehog in Osteoblasts and Its Posttranscriptional Regulation by TGFβ" Endoclinology. 138・5. 1972-1978 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Matsue, M.Noda et al.: "Helix-Loop-Helix Type Transcription Factor,HES-1,Is Expressed in Osteoblastic Cells,SuppressedBy 1,25(OH)_2D_3 And Modulates 1,25(OH)_2D_3 Enhancement of Osteopontin Expression" Bone. 20・4. 329-334 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Liu, M.Noda et al.: "Overexpression of a single helix-loop-helixtype transcription factor,scleraxis,enhances aggrecan gene sxpression in osteoblastic osteosarcoma ROS17/2.8 cells." Journal of Biological Chemistry. 272・47. 29880-29885 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Liu, M.Noda et al.: "Scleraxis is expressed in C2C12 myobalsts and its level is down-regulated by bone morphogenetic protein-2(BMP2)" Journal of Cellular Biochemistry. 67. 1-9 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Ezura, M.Noda et al.: "Identification of a novel suppressive viamin D response sequence in the 5' flanking region of murine ld1 gene." Journal of Biological Chemistry. 272・47. 29865-29872 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] A.Nifuji, M.Noda et al.: "Pertubation of BMP signaling in somitogenesis resulted in vertebral and rib malformation intheaxial skeletal formation." Journal of Bone and Mineral Research. 12・3. 332-342 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Kawauchi, M.Noda et al.: "Messenger RNA Expression of the Genes Encoding Receptors for Bone Morphogenetic Protein(BMP)andTransforming Growth Factor-β(TGF-β) in the Cells from the Posterior Longitudinal Ligament in Cervical Spine" Endocrine. 5・3. 307-314 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Liu, M.Noda et al.: "Sclerotome-related helix-loop-helix type transcription factor(scleraxis)mRNA is expressed in osteoblasts and its level is enhanced by type-β transforming growth factor" Journal of Endocrinology. 151. 491-499 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Matsumoto, M.Noda et al.: "Establishment and characterization of bone marrow stromal cell lines that support osteoclastogenesis" Endocrinology. 136. 4084-4091 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Tamura, M.Noda et al.: "1a,25-Dihydroxyvitamin D3 down-regulates pleiotrophin messenger RNA expression in osteoblast-like cells" Endocrine Journal. 3. 21-24 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Kawauchi, M.Noda et al.: "Fibroblast growth factor enhances expression of TGFβ-stimulated-clone-22 in osteoblast-likecells." Endocrine Journal. 3. 833-837 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Yamashita, A.Nifuji, K.Furuya, Y.Nabeshima and M.Noda: "Elongation of the epiphyseal trabecular bone associated with precocious aging in transgenic mice carrying an insertional mutaiton in Klotho gene locus." Journal of Bone and Mineral Research. (inpress). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Tsuji, Y.Ito and M.Noda: "Perturbation of BMP signaling in somitogenesis resulted in vertebral and rib malformation in the axial skeletal formation." Bone. 22-2. 87-92 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Murakami, A.Nifuji and M.Noda: "Expression of Indiana Hedgehog in Osteoblasts and Its Posttranscriptional Regulation by TGFbeta." Endocrinology. 138-5. 1972-1978 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Matsue, R.Kageyama, D.T.Denhardt and M.Noda: "Helix-Loop-Helix Type Transcription Factor, HES-1, Is Expressed In Osteoblastic Cells, Suppressed By 1,25(OH)_2D_3And Modulates 1,25(OH)_2D_3Enhancement of Osteopontin Expression." Bone. 20,10-4. 329-334 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Liu, H.Watanabe, Y.Yamada, E.Olson, A.Nifuji and M.Noda: "Overexpression of a single helix-loop-helix type transcription factor, scleraxis, enhances aggrecan gene expression in osteoblastic osteosarcoma ROS17/2.8 cells." Journal of Biological Chemistry. 272-47. 29880-29885 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Liu, J.Wozney, A.Nifuji, E.Olson and M.Noda: "Scleraxis is expressed in C2C12 myoblasts and its level is down-regulated by bone morphogenetic protein-2 (BMP2)." Journal of Cellular Biochemistry. 67. 1-9 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Ezura, O.Tournay A.Nifuji and M.Noda: "Identification of a novel suppressive vitamin D response sequence in the 5' flanking region of murine Id1 gene." Journal of Biological Chemistry. 272-47. 29865-29872 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] A.Nifuji, O.Kellerman, Y.Kuboki, J.Wozney and M.Noda: "Perturbation of BMP signaling in somitogenesis resulted in vertebral and rib malformation in the axial skeletal formation." Journal of Bone and Mineral Research. 12-3. 332-342 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Kawa-uchi, K.Furuya, K.Shinomiya, I.Yama-ura, Y.Kurosa, J.M.Wozney, N.Ueno and M.Noda: "Messenger RNA Expression of the Genes Encoding Receptors for Bone Morphogenetic Protein (BMP) and Transforming Growth Factor-beta (TGF-beta) in the Cells from the Posterior Longitudinal Ligament in Cervical Spine" Endocrine. 5. 307-314 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Liu, P.Cserjesi, A.Nifuji, E.N.Olson and M.Noda: "Sclerotome-related helix-loop-helix type transcription factor (scleraxis) mRNA is expressed in osteoblasts and its level is enhanced by type-beta transforming growth factor" Journal of Endocrinology. 151. 491-499 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Matsumoto, M.Tamura, D.T.Denhardt, M.Obinata and M.Noda: "Establishment and characterization of bone marrow stromal cell lines that support osteoclastogenesis" Endocrinology. 136. 4084-4091 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Tamura, F.Ichikawa, R.P.Guillerman, T.F.Deuel and M.Noda: "1 _<alpha>,25-dihydroxyvitamin D_3 down-regulates pleiotrophin messenger RNA expression in osteoblast-like cells" Endocrine. 3. 21-24 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Kawa-uchi, K.Nose and M.Noda: "Fibroblast growth factor enhances expression of TGFbeta-stimulated-clone-22 gene in osteoblast-like cells." Endocrine. 3. 833-837 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Liu, M.Noda et al.: "Scleraxis is expressed in C2C12 myoblasts and its level is down-regulated by bone morphogenetic protein-2 (BMP2)." Journal of Cellular Biochemistry. 67. 1-9 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Liu, M.Noda et al.: "Overexpression of a single helix-loop-helix type transcription factor,scleraxis,enhances aggrecan gene expression in osteoblastic osteosarcoma ROS17/2.8 cells." Journal of Biological Chemistry. 272・47. 29880-29885 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Ezura, M.Noda et al.: "Identification of a novel suppressive vitamin D response sequence in the 5' flanking region of murine ld1 gene." Journal of Biological Chemistry. 272・47. 29865-29872 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] A.Nifuji, M.Noda et al.: "Perturbation of BMP signaling in somitogenesis resulted in vertebral and rib malformation in the axial skeletal formation." Journal of Bone and Mineral Research. 12・3. 332-342 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Matsue, M.Noda et al.: "Helix-Loop-Helix Type Transcription Factor,HES-1,Is Expressed In Osteoblastic Cells,Suppressed By 1.25(OH)_2D_3 And Modulates 1.25(OH)_2D_3 Enhancement of Osteopontin Expression" Bone. 20. 329-334 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] S.Murakami, M.Noda et al.: "Expression of Indiana Hedgehog in Osteoblasts and Its Posttranscriptional Regulation by TGFβ" Endoclinology. 138・5. 1972-1978 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Tsuji, M.Noda et al.: "Perturbation of BMP signaling in somitogenesis resulted in vertebral and rib malformation in the axial skeletal formation." Bone. 22・2. 87-92 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Yamashita, M.Noda et al.: "Elongation of the epiphyseal trabecular bone associated with precocious aging in transgenic mice carrying an insertional mutaiton in Klotho gene locus." Journal of Bone and Mineral Research. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Toshiyuki Kawa-uchi: "Messenger RNA Expression of the Genes Encoding Receptors for Bone Morphogenetic Protein (BMP) and Transforming Growth Factor-β (TGF-β) in the Cells from the Posterior Longitudinal Ligament in Cervical Spine" Endocrine. 5・3. 307-314 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ying Liu: "Sclerotome-related helix-loop-helix type transcription factor (scleraxis) mRNA is expressed in osteoblasts and its level is enhanced by type-β transforming growth factor" Journal of Endocrinology. 151. 491-499 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nobuko Mataga: "Establishment of a Novel Chondrocyte-like Cell Line Derived from Transgenic Mice Harboring the Temperature-Sensitive Simian Virus 40 Large T-Antigen Gene" Journal of Bone and Mineral Research. 11・11. 1646-1654 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shunichi Murakami: "Expression of Indiana Hedgehog in Osteoblasts and Its Posttranscriptional Regulation by TGFβ" Endocrinology. 139(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Mariko Matsue: "Helix-Loop-Helix Type Transcription Factor,HES-1,Is Expressed In Osteoblastic Cells,Suppressed By 1,25(OH)_2D_3 And Modulates 1,25(OH)_2D_3 Enhancement of Osteopontin Expression" Bone. 20(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Matsumoto H.: "Establishment and Characterization of Bone Marrow Stromal Cell Line That Support Osteoclastogenesis." Endocrinology. 136(9). 4048-4091 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tamura M.: "1α,25-dihydroxyvitamin D dwon-regulates pleiotrophin messenger RNA expression in osteoblast-like cells." Endocrine. 3. 21-24 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kawa-uchi T.: "Fibroblast growth factor enhances expression of TGFβ-stimulated-clone-22 gene in osteoblast-like cells." Endocrine. 3. 833-837 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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