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Arole of lipid mediators in chondrocyte

Research Project

Project/Area Number 18591126
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionSt.Marianna University School of Medicine

Principal Investigator

MASUKO Kayo  St.Marianna University School of Medicine, Department of Biochemistry, Assistant Professor (80288208)

Co-Investigator(Kenkyū-buntansha) KATO Tomohiro  St. Marianna University School of Medicine, Department of Biochemistry, Professor (80233807)
NAKAMURA Hiroshi  St. Marianna University School of Medicine, Department of Biochemistry, Docent (80227933)
YUDO Kazuo  St. Marianna University School of Medicine, Institute Medical Science, Associate Professor (60272928)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,190,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordschondrocytes / osteoarthritis / rheumatoid arthritis / lipid mediator / sphingosine / S1P / proteoglycan / prostaglandin / SIP / プロスタグランジンn
Research Abstract

BACKGROUND: Sphingosine-1-phosphate (S1P), a downstream metabolite of ceramide, induces various bioactivities via two distinct pathways: as an intracellular second messenger or through receptor activation. The receptor for S1P (S1PR) is the family of Endothelial differentiation, sphingolipid G-protein-coupled receptor (EDG). We have here attempted to reveal the expression of EDG/S1PR in human articular chondrocytes (HAC), exploring the implications of S1P in cartilage degradation.
METHODS: Articular cartilage specimens were obtained from patients with rheumatoid arthritis (RA), osteoarthritis (OA) or traumatic fracture (representing normal chondrocytes) who underwent joint surgery. Isolated HAC were cultured in vitro by monolayer and stimulated with S1P in the presence or absence of inhibitors of signaling molecules. Stimulated cells and culture supernatants were collected and subjected to analyses using reverse transcription-polymerase chain reaction (MGR), Western blotting, and enzyme-linked immunosorbent assay (ELISA).
RESULTS: All of the tested HAC samples showed positive results in terms of EDG/S1PR expression in basal condition. When HAC was stimulated with S1P, a significant increase in prostaglandin (PG) E2 production was observed together with enhanced expression of cyclooxygenase (COX)-2. S1P stimulated extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) in HAC, and the PGE2 induction was abrogated by PD98059 and SB203580. Pertussis toxin inhibited the PGE2 induction from HAC by SW, suggesting an essential role for Gi protein. S1P also attenuated the expression of proteoglycan aggrecan, a component of cartilage matrix, in HAC at transcriptional
CONCLUSION : It was suggested that the S1P-induced PGE2 was at least in part involved in the aggrecan-suppressing effect of S1P, seeing as COX inhibitors attenuated the effect Accordingly, S1P might play an important role in cartilage degradation in arthritides.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (10 results)

All 2007 2006

All Journal Article (8 results) (of which Peer Reviewed: 4 results) Presentation (2 results)

  • [Journal Article] Sphingosine-1-phosphate attenuates proteoglycan aggrecan expression via production of prostaglandin E2 from human articular chondrocytes2007

    • Author(s)
      Masuko K., et. al.
    • Journal Title

      BMC Musculoskeletal Disorders

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Tryptase enhances release of vascular endothelial growth factor from human osteoarthritic chondrocytes2007

    • Author(s)
      Masuko K., et. al.
    • Journal Title

      Clin Exp Rheumatol 25(6)

      Pages: 860-865

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Sphingosine-1-phosphate attenuates proteoglycan aggrecan expression via production of prostaglandin E2 from human articular chondrocytes.2007

    • Author(s)
      Masuko K, Murata M, Nakamura H, Yudoh K, Nishioka K, Kato T.
    • Journal Title

      BMC Musculoskelet Disord. 20

      Pages: 8-29

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Tryptase enhances release of vascular endothelial growth factor from human osteoarthritic chondrocytes.2007

    • Author(s)
      Masuko K, Murata M, Xiang Y, Nakamura H, Yudoh K, Nishioka K, Beppu M, Kato T.
    • Journal Title

      Clin Exp Rheumatol. 25(6)

      Pages: 860-5

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Sphingosine-1-phosphate attenuates proteoglycan aggrecan expression via production of prostaglandin E2 from human articular chondrocytes2007

    • Author(s)
      Masuko K, et. al.
    • Journal Title

      BMC Musculoskeletal Disorders 8(29)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tryptase enhances release of vascular endothelial growth factor from humanosteoarthritic chondrocytes.2007

    • Author(s)
      Masuko K, et. al.
    • Journal Title

      Clin Exp Rheumatol 25(6)

      Pages: 860-865

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sphingosine-1-phosphate attenuates proteoglycan aggrecan expression via production of prostaglandin E2 from human articular chondrocytes2007

    • Author(s)
      Masuko K, et al.
    • Journal Title

      BMC Musculoskeletal Disorders (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A novel pathway of cartilage degradation : lipid mediators affect chondrocytes2006

    • Author(s)
      Masuko K, et al.
    • Journal Title

      Mod Rheumatol 16(suppl)

      Pages: 142-3

    • Related Report
      2006 Annual Research Report
  • [Presentation] スフィンゴシン1リン酸(S1P)による軟骨変性機構2007

    • Author(s)
      増子 佳世, 他
    • Organizer
      第51回日本リウマチ学会学術集会
    • Place of Presentation
      横浜
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] A role of sphingosine-1-phosphate in cartilage degeneration2007

    • Author(s)
      Masuko K, Murata M, Yudo K, Nakamura H, Kato T.
    • Organizer
      51st Annual Scientific Meeting, Japan College pf Rheumatology.
    • Place of Presentation
      Yokohama
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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