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Mechanism of synovial cell proliferation and osteoclast differentiation in an in vitro model of bone destruction of cultured rheumatoid synovium

Research Project

Project/Area Number 14570433
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionTokai University

Principal Investigator

SUZUKI Yasuo  Tokai University, School of Medicine, Associate Professor, 医学部, 助教授 (90129495)

Co-Investigator(Kenkyū-buntansha) TANIHARA Masao  Nara Institute of Science and Technology, Professor, 物質創成科学研究科, 教授 (50294286)
YAMADA Chiho  Tokai University, School of Medicine, Assistant Researcher, 医学部, 助手 (40317813)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsRHEUMATOID ARTHRITIS / BONE DESTRUCTION / OSTEOCLAST / IN VITRO MODEL / RANKL / RANK / VEGF / SYNOVIOCYTE / TNFα
Research Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory arthritis characterized by bone and cartilage destruction leading to loss of joint function. Characteristic histological features of RA are hyperplasia of synovial lining cells with a dense microvasculature and infiltration of inflammatory mononuclear cells with a formation of lymphoid follicles. Osteoclast is an only bone resorbing cells in the human bone tissues and recent studies demonstrated an involvement of osteoclasts or osteoclast-like cells in the pathogenesis of focal bone erosion in RA. Two factors, receptor activator of NF-KB ligand (RANKL) and macrophage-colony stimulating factor (M-CSF) are essential for the differentiation and activation of osteoclasts. However, the precise mechanism of osteoclast differentiation in the inflamed rheumatoid synovial tissues remains to be established. Recently, we have established a novel in vitro model of bone destruction by rheumatoid synovium^<20)>. This culture system employed osteocl … More ast-like cells differentiated from RA synovial tissue without any inducers. Using the in vitro culture model of bone destruction, we sought to determine what factors are involved in the development of osteoclast-like cells from RA synovium Formation of OC-like cells in the culture of RA synovial tissue was much higher than that in the culture OA synovial tissue and cultured rheumatoid synovium produced higher level of VEGF. VEGF receptor determined imniunohistochemically was expressed on the macrophages and OC like multinucleated cells. VEGF receptor 1-Fc chimeric protein inhibited OC-like cell and pit formation in a dose-dependent manner. Osteoprotegerin (OPG) and TNF receptor II-Fc chimeric protein also inhibited OC formation, but MCSF receptor-Fc chimeric protein was not effective. The RANK peptide that binds to RANKL inhibited OC-like cell formation in the cultured RA synovium.
Our data suggest that both RANKL-dependent and independent signals might be involved in the formation of osteoclasts in the in vitro model of bone destruction. In addition, VEGF might be one of the key mediators of osteoclast-mediated bone destruction by RA synovium. Inhibition of RANKL/RANK and VEGF pathway could be a new strategy for the treatment of RA. Less

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (39 results)

All Other

All Publications (39 results)

  • [Publications] 鈴木康夫: "筋骨格系・結合識疾患:慢性関節リウマチ"日本臨床 臨床統計集(3). Vo.60 増刊. 331-340 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 鈴木康夫, 井手美香子, 野口淳他: "RAに対するDMARD併用療法 MTX追加併用療法"リウマチ科. 27巻. 25-32 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 鈴木康夫: "慢性関節リウマチにおける骨病変"日本臨床. 60巻. 407-417 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 鈴木康夫, 田中千絵, 尾崎承一, 堀田知光: "メトトレキサート(MTX)により誘発されるリンパ増殖性疾患"リウマチ科. 28巻5号. 498-506 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki Y: "Transverse myelopathy in systemic lupus erythematosus"Intern Medicine. 41. 327-328 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 若林孝幸, ジャクソン加奈子, 山田千穂, 鈴木康夫: "骨軟骨破壊に対するMTX療法の現状と今後"Clinical Calcium. 13・6. 764-770 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 鈴木康夫: "ステロイド誘発骨粗鬆症-疫学・病態・予防治療ガイドライン-"Osteoporosis Japan. 11・3. 427-436 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ichikawa Y, Kamatani N, Goto M, Kondo H, Saito T, Yasuo Suzuki, et al.: "Phase II dose ranging study of leflunomide in Japan"J New Remedies & Clinics. 52・7. 891-931 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Chinen N, Tanihara M, Nakagawa M, Shinozaki K, Yamamoto E, Mizushima Y, Yasuo Suzuki: "Action of microparticles of heparin and alginate crosslinked gel when used as injectable artificial matrices to stabilize basic fibroblast growth factor and induce angiogensis by controlling its release."J Biomed Material Res. 67A. 61-68 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 鈴木康夫: "ガイドラインに基づく関節リウマチの新薬物療法戦略 レフルノミド"臨床と薬物治療. 22・12. 1102-1106 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 鈴木康夫: "関節リウマチのMTX療法-我が国の現状とグローバルスタンダード-"Pharma Mdeica. 21・12. 43-47 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 鈴木康夫: "第2回リウマチ性疾患研究会 講演記録集 リウマチの骨破壊と破骨細胞"インターサイエンス(東京). 4-9 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 鈴木康夫: "正しい薬物療法のために 病態生理と薬効薬理から処方せんを見る 骨・関節疾患 -骨粗鬆症, 関節リウマチ-"財団法人 日本薬剤師研修センター編. 3-27 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasuo Suzuki: "Musculoskeletal disorder : Rheumatoid arthritis"Nihon Rinsho. Vol.60 Supple. 331-340 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasuo Suzuki, Mikako Ide, Atushi Noguchi: "Combination DMARD for RA : Additive combination of MTX"Riumachika. Vol.27. 25-32 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasuo Suzuki: "Bone destruction and bone loss in RA"Nihon Rinsho. Vol.60. 407-417 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasno Suzuki, Chie Tanaka, Shoichi Ozaki, Tomomitsu Hotta.: "Methotrexate-associated lyinphoproliferative disorders"Riumachika. 28:5. 498-506 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasuo Suzuki: "Transverse myelopathy in systemic lupus erythematosus"Intern Medisine. 41. 327-328 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takaynki Wakabayashi, Kanako Jackson, Chiho Yamada, Yasuo Suzuki: "Methotrexate for the prevention of bone destruction in rheumatoid arthritis-"Clinical Calcium. Vol.13.No.6. 764-770 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasuo Suzuki: "Corticosteroid-induced osteoporosis-epidemiology, pathogenesis, and guideline for the prevention and treatment-"Osteoporosis Japan. vol 11, No.3. 427-436 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ichikawa Y, Kamatani N, Goto M, Kondo H, Saito T, Yasuo Suzuki, Torikal K, Hashimoto H, Miyasaka N, Yamanaka H, Yamamoto K, Fukao A, Mizushima Y.: "Phase II dose ranging study of leflunomide in Japan"J New Remedies & Clinics. Vol.52, No.7. 891-931 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Chinen N, Tanihara M, Nakagawa M, Shinozaki K, Yamamoto E, Mizushima Y, Yasuo Suzuki: "Action of microparticles of heparin and alginate crosslinked gel when used as injectable artificial matrices to stabilize basic fibroblast growth factor and induce angiogensis by controlling its release."J Biomed Material Res. Vol 67A. 61-68 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasuo Suzuki: "Guideline for the drug treatment of rheumatoid arthritis Leflunomide"Rinsho To Yakubutsuchiryou. Vol.22, No.12. 1102-1106 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasuo Suzuki: "Methotrexate as a global standard of anti-rheumatic drung"Pharma Mdeica. Vol.21, No.12. 43-47 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasuo Suzuki: "Role of osteoclast in bone destruction of RA"2nd conference for Rheumatic Diseases(Interscience(Tokyo)). 4-9 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasuo Suzuki: "Drug Therapy for Bone and Joint Disorders-Osteoporosis and Rheumatoid Arthritis-"Japan Pharmacists Education Center,(Tokyo). 3-27 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 若林孝幸, ジャクソン加奈子, 山田千穂, 鈴木康夫: "骨軟骨破壊に対するMTX療法の現状と今後"Clinical Calcium. 13・6. 764-770 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 鈴木康夫: "ステロイド誘発骨粗鬆症-疫学・病態・予防治療ガイドライン-"Osteoporosis Japan. 11・3. 427-436 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ichikawa Y, Kamatani N, Goto M, Kondo H, Saito T, Yasuo Suzuki, et al.: "Phase II dose ranging study of leflunomide in Japan"J New Remedies & Clinics. 52・7. 891-931 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Chinen N, Tanihara M, Nakagawa M, Shinozaki K, Yamamoto E, Mizushima Y, Yasuo Suzuki: "Action of microparticles of heparin and alginate crosslinked gel when used as injectable artificial matrices to stabilize basic fibroblast growth factor and induce angiogensis by controlling its release."J Biomed Material Res. 67A. 61-68 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 鈴木康夫: "ガイドラインに基づく関節リウマチの新薬物療法戦略レフルノミド"臨床と薬物治療. 22・12. 1102-1106 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 鈴木康夫: "関節リウマチのMTX療法-我が国の現状とグローバルスタンダード-"Pharma Mdeica. 21・12. 43-47 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 鈴木康夫: "第2回リウマチ性疾患研究会 講演記録集 リウマチの骨破壊と破骨細胞"インターサイエンス(東京). 4-9 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Chinen N, Tanihara M, Suzuki Y et al.: "Action of microparticles of heparin and alginate cross-linked gel when used as injectable artificial matrices to stabilize basic fibroblast growth factor and induce angiogenesis by controlling its release"J Biomed Material Res. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Suzuki Y.: "Transverse myelopathy in systemic lupus erythematosus"Intern Medicine. Vol.41, No.4. 327-328 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 鈴木康夫: "筋骨格系・結合識疾患:慢性関節リウマチ"日本臨床 臨床統計集(3). Vo.60増刊. 331-340 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 錦木康夫, 井手美香子, 野口淳他: "RAに対するDMARD併用療法のMTX追加併用療法"リウマチ科. 27巻. 25-32 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 鈴木康夫: "慢性関節リウマチにおける骨病変"日本臨床. 60巻. 407-417 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 鈴木康夫, 田中千絵, 尾崎承一, 堀田知光: "メトトレキサート(MTX)により誘発されるリンパ増殖性疾患"リウマチ科. 28巻5号. 498-506 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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