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Molecular Analysis of PTHrP Receptor in Chondrocytes

Research Project

Project/Area Number 07671599
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionNagasaki University

Principal Investigator

OHTSURU Akira (1996)  Nagasaki University School of Medicine, Assistant Professor, 医学部, 助手 (00233198)

小田 純爾 (1995)  長崎大学, 医学部, 助手 (30253644)

Co-Investigator(Kenkyū-buntansha) 大津留 晶  長崎大学, 医学部, 助手 (00233198)
岩崎 勝郎  長崎大学, 医学部, 教授 (60039542)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordschondrocyte / PTHrP receptor / PTHrP / osteoarthritis / rheumatic arthritis / PTH / 変形性膝関節症 / chondrocyte / cloning
Research Abstract

To elucidate the physiology of parathyroid-hormone-related peptide (PTHrP) in chondrocytes, it is essential to investigate on the molecular mechanism of PTHrP receptor mediated signal transduction because PTHrP knock-out mice developed achondroplasia like deformity. In the present projects, we have concentrated in the receptor-mediated signal transduction and PTHrP expression of various cartilage disease. In the former, we have studied the effect of various fragments of PTHrP in primary culture of rat articular chondrocytes and function of the cell lines transfected PTHrP.In the later, we have analyzed the pathophysiological role of parathyroid-hormone-related peptide (PTHrP) in osteoarthritis and rheumatic arthritis.
The action of exogenously added hPTHrP (1-34), hPTHrP (1-141), hPTHrP (100-114) and hPTH (1-34) on thymidine incorporation, alpha (1) type II collagen gene expression, intracellular cAMP and [Ca^<2+>] i level was similar. Antisense oligonucleotides decreased PTHrP mRNA tra … More nslation specifically inhibited DNA synthesis. These data are speculated that there is no significant difference among exogenously added hPTH and hPTHrP,on the other hand intracellular PTHrP may have a yet unknown biological role, in addition to a classical PTH/PTHrP receptor-mediated function (J Endocrinology 150 : 359-368 1996).
In tissue regeneration of osteoarthritis and rheumatic arthritis, PTHrP is a key cytokine regulated the cell motility and apoptosis (Br J Rheumatol 35 : 1056-1062 1996, J Osteopaedic Res, in press). To further extend the basic research, we have focused on the critical events of chondrocytes induced by abnormal expression of cytokines escaping from physiological regeneration or apoptosis, which can eventually induce gene instability and abnormal cell proliferation. The experimental design is in vivo rat animal model which was implanted with PTHrP producing osteoblast like cell and developed bone matrix formation around the cells (Endocrine J 43 : 527-535 1996). Furthermore, we have applied the antisense PTHrP oligonucleotide therapy against PTHrP producing tumor (Cancer Res 56 : 77-86,1996).
Finally, we acknowledge a support from this grant and a valuable contribution of our post doc fellows and staffs. Less

Report

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

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Okano K et al: "Expression of parathyroid hormone-related peptide in human osteoarthritis." J Osteopaedic Res. (in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tsukazaki T et al: "Parathyroid hormone-related protein ( PTHrP ) action in rat articular chondrocytes : comparison of PTH (1-34), PTHrP (1-34),(1-141),(100-114) and antisense oligonucleotide." J Endocrinol. 150. 359-368 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Motomura K et al: "Osteogenic action of parathyroid hormone-related peptide (1-141) in rat ROS cells." Endocrine J. 43. 527-535 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akino K et al: "Antisense inhibition of parathyroid hormone-related peptide gene expression reduces malignant rat pituitary tumor progression and matestases." Cancer Res. 56. 77-86 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Okano et al: "Parathyroid hormone-related peptide in synovial fluid is a novel marker of disease activity in rheumatoid arthritis." Br J Rheumatol. 35. 1056-1062 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakashima et al: "Expression of parathyroid hormone-related peptide (PTHrP) and PTH/PTHrP receptor in giant cell tumor of tendon sheath." J Pathol. 180. 80-84 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yamashita S et al: "Oncogenesis and Molecular Biology on Pituitary Tumors" ed.by Melmed S, Front Horm Res.Basel, Karger, 18 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tsukazaki T,et al: "Developmental expression of parathyroid hormone-related protein in rat aritcular cartilage" Calcif Tissues Int. 57. 196-200 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Okano K,et al: "Parathyroid hormone-related peptide in synovial fluid is a novel marker of disease activity in rheumatoid arthritis" Br J Rheumatol. 35. 1056-1062 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tsukazaki T,et al: "Parathyroid hormone-related protein (PTHrP) action in rat articular chondrocytes : Comparison of PTH (1-34), PTHrP (1-34), (1-141), (100-114) and Antisense Oligonucleotides against PTHrP" J Endocrinol. 150. 359-368 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Motomura K,et al: "Autocrine/paracrine role of parathyroid hormone-related peptide (1-141) on osteogenic properties in rat ROS cells" Endocrine J. 43. 527-535 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akino K,et al: "Antisense inhibition of parathyroid hormone-related peptide gene expression reduces malignant rat pituitary tumor progression and metastases" Cancer Res. 56. 77-86 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Okano K,et al: "Expression of parathyroid hormone-related peptide in human osteoarthritis" J Osteopaedic Res. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sugiyama M,et al: "Localization of apoptosis and expression of apoptosis related proteins in the synovium of patients with rheumatoid arthritis" Annals Rheum Dis. 55. 442-449 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Makashima M,et al: "Expression of parathyroid hormone-related peptide (PTHrP) and PTH/PTHrP receptor in giant cell tumor of tendon sheath" J Pathol. 180. 80-84 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Okano K et al: "Expression of parathyoid hormone-related peptide in human osteoarthritis." J Osteopaedic Res. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tsukazaki T et al: "Parathyroid hormone-related protein (PTHrP) action in rat articular chondrocytes:comparison of PTH (1-34) ,PTHrP (1-34),(1-141),(100-114) and antisense oligonucleotides." J Endocrinol. 150. 359-368 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Motomura K et al: "Osteogenic action of parathyroid hormone-related peptide (1-141) in rat ROS cells." Endocrine J. 43. 527-535 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Akino K et al: "Antisense inhibition of parathyroid hormone-related-peptide gene expression reduces malignant rat pituitary tumor progression and metastases." Cancer Res. 56. 77-86 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Okano et al: "Parathyroid hormone-related peptide in synovial fluid is a novel marker of disease activity in rheumatoid arthritis." Br J Rheumatol. 35. 1056-1062 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakashima et al: "Expression of parathyroid hormone-related peptide (PTHrP) and PTH/PTHrP receptor in giant cell tumor of tendon sheath." J Pathol. 180. 80-84 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamashita S et al: "Oncogenesis and Molecular Biology on Pituitary Tumors" ed.by Melmed S,Front Horm Res.Basel,Karger, 18 (1996)

    • Related Report
      1996 Annual Research Report

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

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