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Role of VEGF in osteoclast-mediated bone destruction in rheumatoid arthritis and

Research Project

Project/Area Number 16590997
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 InstitutionTokai University

Principal Investigator

SUZUKI Yasuo  Tokai Univ., Sch of Med, Professor, 医学部, 教授 (90129495)

Co-Investigator(Kenkyū-buntansha) YAMADA Chiho  Tokai Univ., Sch of Med, Assistant Researcher, 医学部, 助手 (40317813)
MOCHIDA Joji  Tokai University, Sch of Med., Professor, 医学部, 教授 (50174347)
TANIHARA Masao  Nara Institute of Tech., Professor, 教授 (50294286)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsRHEUMATOID ARTHRITIS / SYNOVIAL MACROPHAGES / OSTEOCLASTS / VEGF / BONE DESTRUCTION / VEGF RECEPTOR PEPTIDE / EXPERIMENTAL ARTHRITIS / TNFα / 血管内皮細胞
Research Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory arthritis characterized by bone and cartilage destruction leading to loss of joint function. 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. Recently, we have established a novel in vitro model of bone destruction by rheumatoid synovium. Two factors, receptor activator of NF-κB ligand (RANKL) and macrophage-colony stimulating factor (M-CSF) are essential for the differentiation and activation of osteoclasts. However, inflammatory cytokines, such as TNF and IL-1 stimulate osteoclast formation, activation and survival by RANKL-independent mechanisms. Such process might be more important in inflammatory arthritis.
Previous our data suggest that both RANKL-dependent and independent process are involved in in vitro model of bone destruction by cultured RA synovium. In addition to inflam … More matory cytokines and RANKL, vascular endothelial growth factor (VEGF) might play a key role in osteoclast formation since the formation of RA synovium-derived osteoclasts was inhibited by VEGF receptor-Fc chimeric protein.
To clarify each role of RANKL/osteoprotegerin system, TNF, and VEGF in osteoclast-mediated bone resorption by RA synovium, we have determined the expression of mRNA of these proteins by RT-PCR during the course of culture. The cultured cells exhibited a remarkable 100 fold increase in VEGF/β-actin mRNA level by the 16^<th> culture day. The level of TNFα mRNA also increased 5-fold at the 2nd culture day. Although the RANKLmRNA expression level did not show a significant change, OPGmRNA expression decreased remarkably at the 3rd week of culture when a marked osteoclast formation was observed.
Our data suggest that imbalance of RANKL/OPG might be important in the formation of osteoclasts from th e cultured rheumatoid synovium. In addition to RNAKL/OPG system, VEGF and TNF were also involved in osteoclast-mediated bone destruction by RA synovium. Inhibition of RANKL and VEGF pathway could be a new strategy for the treatment of RA. To block VEGF signals, we have designed and synsethized 3 types of VEGF receptor peptides and the experiments to see the effect of these peptides on experimental arthritis induced by monoclonal antibodies against type II collagen is now undergoing. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (32 results)

All 2006 2005 2004

All Journal Article (29 results) Book (3 results)

  • [Journal Article] Guidelines on the management and treatment of glucocorticoid-induced osteoporosis of the Japanese Society for Bone and Mineral Research(2004).2005

    • Author(s)
      Nawata H, Soen S, Takayanagi R, Tanaka I, Takaoka K, Fukunaga M, Matsumoto T, Suzuki Y, Tanaka H, Fujiwara S, Miki T, Sagawa A, Mishizawa Y, Seino Y.
    • Journal Title

      J Bone Miner Metab 23(1)

      Pages: 105-109

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Whole genome association study of rheumatoid arthritis using 27 039 microsatellites.2005

    • Author(s)
      Tamiya G, Shinya M, Imasnishi T, Suzuki Y, et al.
    • Journal Title

      Human Mol Gen 14(16)

      Pages: 2305-2321

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Therapeutic effects of the combination of methotrexate and bucillamine in early rheumatoid arthritis : a multicenter, double-blind, randomized controlled study.2005

    • Author(s)
      Ichikawa Y, Saito T, Yamanaka H, Akizuki M, Kondo H, Kobayashi S, Oshima H, Kawai S, Hama N, Yamada H, Mimori T, Amano K, Tanaka Y, Matsuoka Y, Yamamoto S, Matsubara T, Murata N, Asai T, Suzuki Y.
    • Journal Title

      Mod Rheumatol 2005;15 : 323-328 15(2)

      Pages: 323-328

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 関節リウマチを取り巻く新しい環境『メトトレキサートの臨床応用の実際』2005

    • Author(s)
      鈴木康夫, 若林孝幸, ジャクソン加奈子, 山田千穂
    • Journal Title

      痛みと臨床 5(1)

      Pages: 25-33

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Clinical application of methotrexate for rheumatoid arthritis.2005

    • Author(s)
      Suzuki Y., Wakabayashi T, Jackson K, Yamada C.
    • Journal Title

      Itami-to-Rinsho 5

      Pages: 25-33

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Methotrexate for the treatment of rheumatoid arthritis.2005

    • Author(s)
      Suzuki Y., Wakabayashi T, Jackson K.
    • Journal Title

      Nihon Rinsho 63(Suppl 1)

      Pages: 498-502

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Methotreaxe for immunological disorders.2005

    • Author(s)
      Suzuki Y.
    • Journal Title

      Nihon Rinsho 63(Suppl 5)

      Pages: 700-707

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Guidelines on the management and treatment of glucocorticoid-induced osteoporosis of the Japanese Society for Bone and Mineral Research (2004)2005

    • Author(s)
      Nawata H, Soen S, Takayanagi R, Tanaka I, Takaoka K, Fukunaga M, Matsumoto T, Suzuki Y, Tanaka H, Fujiwara S, Miki T, Sagawa A, Mishizawa Y, Seino Y.
    • Journal Title

      J Bone Miner Metab 23

      Pages: 105-109

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Whole genome association study of rheumatoid arthritis using 27039 microsatellites.2005

    • Author(s)
      Tamiya G, Shinya M, Imasnishi T, Ikuta T, Makino S, Okamoto K, Furugaki K, Matsumoto T, Mano S, Ando S, Nozaki Y, Yukawa W, Nakashige R, Yamaguchi D, Ishibayashi H, Yonekura M, Nakamai Y, Takayama S, Endo T, Saruwtari T, Yagura M, Yoshikawa Y, Fuujimoto K, Oka A, Chiku S, Linsei SEV, Giphart MJ, Kulski JK, Fukazawa T, Hashimoto H, Kimura M, Hoshina Y, Suzuki Y, Hotta T, Mochida J, Minezaki T, Komai K, Shinozawa S, TaniguchiA, Yamanaka H, Kamatani N, Gojobori T, Bahram S, Inoko H
    • Journal Title

      Human Mol Gen 14

      Pages: 2305-2321

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Therapeutic effects of the combination of methotrexate and bucillamine in early rheumatoid arthritis : a multicenter, double-blind, randomized controlled study.2005

    • Author(s)
      Ichikawa Y, Saito T, Yamanaka H, Akizuki M, Kondo H, Kobayashi S, Oshima H, Kawai S, Hama N, Yamada H, Mimori T, Amano K, Tanaka Y, Matsuoka Y, Yamamoto S, Matsubara T, Murata N, Asai T, Suzuki Y.
    • Journal Title

      Mod Rheumatol 15

      Pages: 323-328

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Guidelines on the management and treatment of glucocorticoid-induced osteoporosis of the Japanese Society for Bone and Mineral Research (2004).2005

    • Author(s)
      Nawata H, Soen S, Takayanagi R, Tanaka I, Takaoka K, Fukunaga M, Matsumoto T, Suzuki Y, Tanaka H, Fujiwara S, Miki T, Sagawa A, Mishizawa Y, Seino Y.
    • Journal Title

      J Bone Miner Metab 23(1)

      Pages: 105-109

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Therapeutic effects of the combination of methotrexate and bucillamine in early rheumatoid arthritis : a multicenter, double-blind, randomized controlled study.2005

    • Author(s)
      Ichikawa Y, Saito T, Yamanaka H, Akizuki M, Kondo H, Kobayashi S, Oshima H, Kawai S, Hama N, Yamada H, Mimori T, Amano K, Tanaka Y, Matsuoka Y, Yamamoto S, Matsubara T, Murata N, Asai T, Suzuki Y.
    • Journal Title

      Mod Rheumatol 15(2)

      Pages: 323-328

    • Related Report
      2005 Annual Research Report
  • [Journal Article]2005

    • Author(s)
      鈴木康夫, 若林孝幸, 小宮喜代里, 齋藤榮子, 野口淳
    • Journal Title

      リウマチ科 34(5)

      Pages: 474-480

    • Related Report
      2005 Annual Research Report
  • [Journal Article] メトトレキサートをいかに上手に使用するか2005

    • Author(s)
      鈴木康夫
    • Journal Title

      Medicina 42(5)

      Pages: 793-795

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Vascular endothelial growth factor plays a key role in osteo-clastic bone destruction by cultured rheumatoid synovium.2004

    • Author(s)
      Itoh G, Nakagawa M, Ozaki S, Suzuki Y.
    • Journal Title

      Clinical Rheumatol. 16

      Pages: 11-19

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Novel heparin/alginate gel combined with basic fibroblast growth factor promotes nerve regeneration in rat sciatic nerve2004

    • Author(s)
      Ohta M, Suzuki Y, Chou H, Ishikawa N, Suzuki S, Tanihara M, Suzuki Y, Mizushima Y, Dezawa M, Ide C.
    • Journal Title

      J Biomed Mater Res 71A(4):

      Pages: 661-668

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Vascular endothelial growth factor plays a key role in osteoclastic bone destruction by cultured rheumatoid synovium.2004

    • Author(s)
      Itoh G, Nakagawa M, Ozaki S, Suzuki Y.
    • Journal Title

      Clinical Rheumatol 16

      Pages: 11-19

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Methotrexate for the treatment of rheumatoid arthritis2004

    • Author(s)
      Suzuki Y.
    • Journal Title

      Igaku no Ayumi 209

      Pages: 827-832

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Secondary osteoporosis in rheumatoid arthritis2004

    • Author(s)
      Suzuki Y.
    • Journal Title

      The Bone 18

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Adverse effects of antirheumatic drugs. Malignancy and teratogenicity2004

    • Author(s)
      Suzuki Y., Wakabayashi T, Jackson K.
    • Journal Title

      Riumach-ka 32

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Pathogenesis and management of glucocorticoid- induced osteoporosis.2004

    • Author(s)
      Suzuki Y.
    • Journal Title

      Medical Practice 21

      Pages: 1695-1699

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Administration of folic acid with methotrexate therapy in rheumatoid arthritis.2004

    • Author(s)
      Suzuki Y., Wakabayashi T, Jackson K.
    • Journal Title

      Riumachi-ka 32

      Pages: 293-300

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Novel heparin/alginate gel combined with basic fibroblast growth factor promotes nerve regeneration in rat sciatic nerve2004

    • Author(s)
      Ohta M, Suzuki Y, Chou H, Ishikawa N, Suzuki S, Tanihara M, Suzuki Y., Mizushima Y, Dezawa M, Ide C.
    • Journal Title

      J Biomed Mater Res 71A(4)

      Pages: 661-668

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Vascular endothelial growth factor plays a key role in osteoclastic bone destruction by cultured rheumatoid synovium.2004

    • Author(s)
      Itoh G, Nakagawa M, Ozaki S, Suzuki Y.
    • Journal Title

      Clinical Rheumatol. 16

      Pages: 11-19

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Novel heparin/alginate gel combined with basic fibroblast growth factor promotes nerve regeneration in rat sciatic nerve2004

    • Author(s)
      Ohta M, Suzuki Y, Chou H, Ishikawa N, Suzuki S, Tanihara M, Suzuki Y, Mizushima Y, Dezawa M, Ide C.
    • Journal Title

      J Biomed Mater Res 171A(4):

      Pages: 661-668

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 新しい抗リウマチ薬-レフルノミド-2004

    • Author(s)
      鈴木康夫, 崎山加奈子, 若林孝幸, ジャクソン加奈子, 山田千穂
    • Journal Title

      リウマチ科 31・3

      Pages: 427-436

    • Related Report
      2004 Annual Research Report
  • [Journal Article] メトトレキサートの使い方と副作用への対処法2004

    • Author(s)
      鈴木康夫
    • Journal Title

      医学のあゆみ 209,10

      Pages: 827-832

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 続発性骨粗鬆症-関節リウマチ-2004

    • Author(s)
      鈴木康夫
    • Journal Title

      The Bone 18.3

      Pages: 327-331

    • Related Report
      2004 Annual Research Report
  • [Journal Article] RAに対するメトトレキサート療法における葉酸使用法2004

    • Author(s)
      鈴木康夫, 若林孝幸, ジャクソン加奈子
    • Journal Title

      リウマチ科 32.3

      Pages: 293-300

    • Related Report
      2004 Annual Research Report
  • [Book] 抗リウマチ薬の選び方と使い方(分担執筆) 抗リウマチ薬各論 メトトレキサート、レフルノミド、ミゾリビン2006

    • Author(s)
      鈴木康夫
    • Publisher
      南弘堂(東京)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 抗リウマチ薬の選び方と使い方(分担執筆)抗リウマチ薬各論 メトトレキサート、レフルノミド、ミゾリビン2006

    • Author(s)
      鈴木康夫
    • Publisher
      南弘堂(東京)
    • Related Report
      2005 Annual Research Report
  • [Book] ステロイド骨粗鬆症の治療マニュアルステロイド骨粗鬆症治療の基本疫学と病態(日本骨粗鬆症学会企画 名和田 新編)2004

    • Author(s)
      鈴木康夫
    • Total Pages
      7
    • Publisher
      ライフサイエンス出版
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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