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2001 Fiscal Year Final Research Report Summary

Intracellulan signal : ry pathways involving bone destruction

Research Project

Project/Area Number 12671397
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionThe University of Tokyo

Principal Investigator

NAKAMURA Ichiro  Dept of Orthop surg, The University of Tokyo, Instractor, 医学部・附属病院, 助手 (30323596)

Co-Investigator(Kenkyū-buntansha) ODA Hiromi  Dept of Orthop surg, The University of Tokyo, Associate prof, 医学部・附属病院, 助教授 (60101698)
TANAKA Sakae  Dept of Orthop surg, The University of Tokyo, Instractor, 医学部・附属病院, 助手 (50282661)
Project Period (FY) 2000 – 2001
Keywordsostooclast / RANKL / RANK / rheumatoid arthritis,
Research Abstract

To clarify the mechanism by which osteoclasts are formed in culture of rheumatoid synoviocytes by exploring the involvement of receptor activator of nuclear factor kappaB ligand (RANKL). RANKL expression was examined by Northern blotting in synovial tissues from 5 rheumatoid arthritis (RA) patients and tissues from patients with osteoarthritis (OA). RANKL expression and the ability of synovial fibroblasts to support osteoclastogenesis were investigated in coculture with PBMC in the presence or absence of 1, 25(OH)2D3, and soluble RANKL/ODF and osteoprotegerin (OPG) were measured by enzyme-linked immunosorbent assay. The effects of OPG on the osteoclastogenesis in the primary culture of rheumatoid synoviocytes and the coculture system were determined. Synovial fibroblasts did not induce osteoclastogenesis when separately cocultured with PBMC. Northern blotting revealed that RANKL/ODF was highly expressed in all tissues from RA and GCT patients, but not from OA or OS patients. Cultured rheumatoid synovial fibroblasts efficiently induced osteoclastogenesis in the presence of 1, 25(OH)2D3, which was accompanied by up-regulated expression of RANKL and decreased production of OPG/OCIF. Osteoclastogenesis from synoviocytes was dose-dependently inhibited by OPG. CONCLUSION : RANKL/ODF expressed on synovial fibroblasts is involved in rheumatoid bone destruction by inducing osteoclastogenesis and would therefore be a good therapeutic target.

  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] Aiichiro Yamamoto et al.: "Requirement of both NF-kB and JNK pathway for osteoclast-genesis induced by RANKL"J. Bone. Miner. Res.. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Tanaka et al.: "The osteoclast : a potential therapeutic target of bone and joint destruction in rheumatoid arthritis"Modern Rheumatology. 11. 177-183 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Takayanagi et al.: "Receptor activator of nuclear factor KB ligand/osteoclast differentiation factor is involved in osteoclastogenesis"Arthritis Rheum. 43. 259-269 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Aiichiro Yamamoto, Tsuyoshi Miyazaki, Yuho Kadono, Hiroshi Takayanagi, Toshiki Miura, Kenji Wakabayashi, Hiroshi Nishina, Toshiaki Katada, Hiromi Oda, Kozo Nakamura, and Sakae Tanaka: "Requirement of Both NFB and JNK Pathways for Osteoclastogenesis Induced by Receptor Activator of NF- B Ligand (RANKL)"J. Bone Miner. Res. in press. (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S Tanaka, K Nakamura, H Oda: "The osteoclast : a potential therapeutic target of bone and joint destruction in rheumatoid arthritis"Modern Rhematology. 11. 177-183 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H Takayanagi, H Iizuka, T Juji, T Nakagawa, A Yamamoto, T Miyazaki, Y Koshihara, H Oda, K Nakamura, S Tanaka: "Receptor activator of nuclear factor kB ligand/ Osteoclast differentiation factor is involved in osteoclastogenesis from synoviocytes in rheumatoid arthritis"Arthritis Rheum. 43. 259-269 (2000)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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