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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 (2001)  Dept of Orthop surg, The University of Tokyo, Instractor, 医学部・附属病院, 助手 (30323596)

清水 学 (2000)  東京大学, 医学部・附属病院, 助手 (60313136)

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)
仲村 一郎  東京大学, 医学部・附属病院, 助手 (30323596)
河野 慎次郎  東京大学, 医学部・附属病院, 助手 (40333463)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsostooclast / RANKL / RANK / rheumatoid arthritis, / 破骨細胞数 / TRAF6
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.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Onodera S, Nishihira J, Iwabuchi K, Koyama Y, Yoshida K, Tanaka S, Minami A.: "Macrophage migration inhibitory factor up-regulates matrix metalloproteinase-9 and -13 in rat osteoblasts. Relevance to intracellular signaling pathways"Journal of Biological Chemistry. (In press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamoto A, Miyazaki T, Kadono Y, Takayanagi H, Miura T, Wakabayashi K, Nishina H, Katada T, Oda H, Hakamura K, Tanaka S.: "Requirement of Both NF- B and JNK Pathways for Osteoclastogenesis Induced by Receptor Activator of NF- B Ligand (RANKL)"Journal of Bone and Mineral Research. (In press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Mochizuki T, Asai A, Saito N, Tanaka S, Katagiri H, Asano T, Nakane M, Tamura A, Kuchino Y, Kitanaka C, Kirino T: "Akt protein kinase inhibits non-apoptotic programmed cell death induced by ceramide"Journal of Biological Chemistry. 277. 2709-2797 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobayashi N, Kadono Y, Naito A, Matsumoto K, Yamamoto T, Tanaka S, Inoue J-1: "Segregation of TRAF6-mediated signaling pathways clarifies its role in osteoclastogenesis"EMBO Journal. 20. 1271-1280 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 田中 栄: "破骨細胞およびその前駆細胞への遺伝子導入"日本骨代謝学会雑誌. 19. 76-79 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 田中 栄: "破骨細胞機能制御におけるc-Srcシグナルの役割"医学のあゆみ. 198. 569-573 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 田中 栄(松本俊夫編): "新・分子骨代謝学と骨粗鬆症 「破骨細胞の機能とその調節」"メジカルレビュー社. 511 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 田中 栄(松本俊夫編): "新臨床医のための分子医学シリーズ 骨・軟骨代謝と注目の骨疾患 「炎症性疾患と骨」"羊土社. 179 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshida Y.,Tanaka S. et al.: "Segregation of TRAFG-mediated signaling pathways clarifies its role in osteoclastogenesis."EMBO J.. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kobayashi N.,Tanaka S. et al.: "Negative regulation of BMP/Smad signaling by Tob in osteoblasts."Cell. 103. 1085-1097 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakagawa T.,Tanaka S. et al.: "Overexpression of the csk gene suppresses tumor metastasis in vivo."Int.J.Cancer. 88. 384-391 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mlura T.,Tanaka S. et al.: "Partial functional recovery of paraplegic rat by adenovirus-mediated gene delivery of constitutively active MEKI."Exp.Neurol.. 166. 115-126 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyazaki T.,Tanaka S. et al.: "Reciprocal Role of ERK and NF-κB pathways in survival and activation of osteoclasts."J.Cell Biol.. 148. 333-342 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takayanagi H.,Tanaka S. et al.: "Receptor activator of nuclear factor κB ligand/Osteoclast differentiation factor is involved in osteoclastogenesis from synoviocytes in rheumatoid arthritis."Arthritis Rheum.. 43. 259-269 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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