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Role of MIF in wear particle-induced oeteolysis and its regulation by MIF-DNA vaccination

Research Project

Project/Area Number 19591746
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionHokkaido University

Principal Investigator

ONODERA Shin  Hokkaido University, 大学院・医学研究科, 助教 (00359481)

Co-Investigator(Kenkyū-buntansha) YOSHIKAZU Koyama  北海道情報大学, 経営情報学部, 教授 (90186841)
KAZUHARU Irie  北海道医療大学, 歯学部, 講師 (70223352)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywordsマクロファージ遊走阻止因子 / 磨耗粉 / 骨溶解 / DNAワクチン / in vivo イメージング / in vivoイメージング / 骨吸収
Research Abstract

人工関節置換術後に問題となる磨耗粉誘発性骨溶解(オステオライシス)における、マクロファージ遊走阻止因子(MIF)の関与をマウス頭頂骨オステオライシスモデルを用いて検討した。チタン粉負荷によりMIF mRNAの発現は亢進し、MIFノックアウトマウスでは野生型マウスに比べ炎症性サイトカイン発現亢進・オステオライシスともに有意に少なかった。
MIF中和抗体を惹起するMIF DNAワクチン接種により炎症性サイトカイン発現亢進は若干抑制されたが有意差はなかった。
ポリエチレン粉負荷による炎症をNFκB/luciferaseトランスジェニックマウスを用いてin vivoイメージングにより可視化した。発光定量値は炎症性サイトカインmRNA相対量、骨吸収マーカー値と正の相関を示し、このシステムは各種particleの炎症・骨吸収惹起性やオステオライシスの薬物療法のin vivo評価に有用と思われた。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (36 results)

All 2009 2008 2007

All Journal Article (21 results) (of which Peer Reviewed: 21 results) Presentation (15 results)

  • [Journal Article] A soluble factor (EMMPRIN) in exudate influences knee motion after total arthroplasty2009

    • Author(s)
      OnoderaJ, Onodera S, Kondo E, Betsuyaku T, Yasuda K
    • Journal Title

      Knee Surg Sports Traumatol Arthrosc 17(3)

      Pages: 298-304

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Deletion of macrophage migration inhibitory factor attenuates neuronal death and promotes functional recovery after compression-induced spinal cord injury in mice2009

    • Author(s)
      NishioY, Koda M, Hashimoto M, Kamada T, Koshizuka S, Yoshinaga K, Onodera S, Nishihira J, Okawa A, Yamazaki M
    • Journal Title

      Acta Neuropathol 117(3)

      Pages: 321-8

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] A soluble factor (EMMPRIN) in exudate influences knee motion after tot al arthroplasty2009

    • Author(s)
      Onodera J
    • Journal Title

      Knee Surg Sports Traumatol Arthrosc 17

      Pages: 298-304

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deletion of macrophage migration inhibitory factor attenuates neuronal death and promotes functional recovery after compression-induced spinal cord iniury in mice2009

    • Author(s)
      Nishio Y
    • Journal Title

      Acta Neuropathol. 117

      Pages: 321-328

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Novel Double-Network Hydrogel Induces Spontaneous Articular Cartilage Regeneration in vivo in a Large Osteochondral Defect2008

    • Author(s)
      YasudaK, Kitamura N, Gong JP, Arakaki K, Kwon HJ, Onodera S, Chen YM, Kurokawa T, Kanaya F, Ohmiya Y, Osada Y
    • Journal Title

      Macromol Biosci 9(4)

      Pages: 307-316

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel DNA vaccine targeting macrophage migration inhibitory factor improves the survival of mice with sepsis2008

    • Author(s)
      TohyamaS, Onodera S, Tohyama H, Yasuda K, Nishihira J, Mizue Y, Hamasaka A, Abe R, Koyama Y
    • Journal Title

      Gene Therapy 15(23)

      Pages: 1513-1522

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Active immunization against macrophage migration inhibitory factor using a novel DNA vaccine prevents ovariectomy-induced bone loss in mice2008

    • Author(s)
      Onodera S, Oshima S, Nishihira J, Yasuda K, Tohyama H, Irie K, Koyama Y
    • Journal Title

      Vaccine 26(6)

      Pages: 829-836

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Local administration of interleukin-1 receptor antagonist inhibits deterioration of mechanical properties of the stress-shielded patellar tendon2008

    • Author(s)
      MiyatakeS, Tohyama H, Kondo E, Katsura T, Onodera S, Yasuda K
    • Journal Title

      J Biomech 41(4)

      Pages: 884-889

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Biological responses of novel high-toughness double network hydrogels in muscle and the subcutaneous tissues2008

    • Author(s)
      Tanabe Y, Yasuda K, Azuma C, Taniguro H, Onodera S, Suzuki A, Chen YM, Gong JP, Osada Y
    • Journal Title

      J Mater Sci Mater Med 19(3)

      Pages: 1379-1387

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ex vivo supplementation of TGF-beta1 enhances the fibrous tissue regeneration effect of synovium-derived fibroblast transplantation in a tendon defect : a biomechanical study2008

    • Author(s)
      Okamoto S, Tohyama H, Kondo E, Anaguchi Y, Onodera S, Hayashi K, Yasuda K
    • Journal Title

      Knee Surg Sports Traumatol Arthrosc 16(3)

      Pages: 333-339

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel DNA vaccine targeting macrophage migration inhibitory factor i improves the survival of mice with sepsis2008

    • Author(s)
      Tohyama S
    • Journal Title

      Gene Therapy 15

      Pages: 1513-1522

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Novel Double-Network Hydrogel Induces Spontaneous Articular Cartilage Regeneration in vivo in a Large Osteochondral Defect2008

    • Author(s)
      Yasuda K
    • Journal Title

      Macromol Biosci. 9

      Pages: 307-316

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ex vivo supplementation of TGF-betal enhances the fibrous tissue regene-ation effect of synovium-derived fibroblast transplantation in a tendon defect: a biomechanical study.2008

    • Author(s)
      Okamoto S
    • Journal Title

      Knee Surg Sports Traumatol Arthrosc. 16

      Pages: 333-339

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biological responses of novel high-toughness double network hydrogels in muscle and the subcutaneous tissues.2008

    • Author(s)
      Tanabe Y
    • Journal Title

      J Mater Sci Mater Med. 19

      Pages: 1379-1387

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Local administration of interleukin-1 receptor antagonist inhibits deterioration of mechanical properties of the stress-shielded patellar tendon.2008

    • Author(s)
      Miyatake S
    • Journal Title

      J Biomech. 41

      Pages: 884-889

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Active immunization against macrophage migration inhibitory factor using a novel DNA vaccine prevents ovariectomy-induced bone loss in mice.2008

    • Author(s)
      Onodera S
    • Journal Title

      Vaccine. 26

      Pages: 829-836

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Total knee arthroplasty with cruciate-retention type alumina ceramic condylar prosthesis2007

    • Author(s)
      YasudaK, Onodera S, Kondo E, Kitamura N, Inoue M
    • Journal Title

      Techniques in Knee Surgery 6(4)

      Pages: 213-219

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] The Proinflammatory Cytokine Macrophage Migration Inhibitory Factor Regulates Glucose Metabolism during Systemic Inflammation2007

    • Author(s)
      AtsumiT, Cho YR, Leng L, McDonald C, Yu T, Danton C, Hong EG, Mitchell RA, Metz C, Niwa H, Takeuchi J, Onodera S, Umino T, Yoshioka N, Koike T, Kim JK, Bucala R
    • Journal Title

      J Immunol 179(8)

      Pages: 5399-5406

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bleeding from the bone marrow enhances remodeling of the in situ frozen-thawed anterior cruciate ligament2007

    • Author(s)
      Yasuda K, Sakai T, Kondo E, Onodera S
    • Journal Title

      Clin Biomechanics 22(8)

      Pages: 941-949

    • NAID

      120000955811

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bleeding from the bone marrow enhances remodeling of the in situ froze n-thawed anterior cruciate ligment.2007

    • Author(s)
      Yasuda K
    • Journal Title

      Clin Biomechanics 22

      Pages: 941-949

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Proinflammatory Cytokine Macrophage Migration Inhibitory Factor Regulates Glucose Metabolism during Systemic Inflammation.2007

    • Author(s)
      Atsumi T
    • Journal Title

      J Immunol. 179

      Pages: 5399-5406

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] ポリエチレン微粒子により惹起される異物性炎症反応のバイオイメージングによる可視化2009

    • Author(s)
      小野寺伸
    • Organizer
      平成20年度厚生労働科学研究費補助金化学物質リスク研究事業「ナノ微粒子体内動態可視化法の開発」第4回研究成果発表会
    • Place of Presentation
      苫小牧市、ホテルニドム
    • Year and Date
      2009-02-21
    • Related Report
      2008 Annual Research Report
  • [Presentation] 新規DNAキャリア分子を用いたアンチセンス核酸療法の確立とその関節炎モデルマウスに対する効果2008

    • Author(s)
      小野寺 伸
    • Organizer
      第23回日本整形外科学会基礎学術集会
    • Place of Presentation
      京都市
    • Year and Date
      2008-10-25
    • Related Report
      2008 Final Research Report
  • [Presentation] 新規DNAキャリア分子を用いたアンチセンス核酸療法の確立とその関節炎モデルマウスに対する効果2008

    • Author(s)
      小野寺伸
    • Organizer
      第23回日本整形外科学会基礎学術集会
    • Place of Presentation
      京都市、国立京都国際会館
    • Year and Date
      2008-10-25
    • Related Report
      2008 Annual Research Report
  • [Presentation] Development of a novel DNA vaccine targeting macrophage migration inhibitory factor and its efficacy on murine models of inflammatory diseases2008

    • Author(s)
      Onodera S
    • Organizer
      2^<nd> World Conference on Magic Bullets
    • Place of Presentation
      Nurnberg, Germany
    • Year and Date
      2008-10-04
    • Related Report
      2008 Final Research Report
  • [Presentation] Development of a novel DNA vaccine targeting macrophage migration inhibitory factor and its efficacy on murine models of inflammator diseases2008

    • Author(s)
      Onodera S
    • Organizer
      2^<nd> World Conference on Magic Bullets
    • Place of Presentation
      ドイツニュルンベルグ市Georg-Simon-Ohm-Hochschule fur angewandte Wissenschaften-Fachhochschule Nurnberg
    • Year and Date
      2008-10-04
    • Related Report
      2008 Annual Research Report
  • [Presentation] 関節リウマチに対するアンチセンスストラテジー2008

    • Author(s)
      小野寺 伸
    • Organizer
      「β1,3グルカンと核酸医薬DDSおよび免疫学との接点」第1回研究会
    • Place of Presentation
      札幌市
    • Year and Date
      2008-07-22
    • Related Report
      2008 Final Research Report
  • [Presentation] 関節リウマチに対するアンチセンスストラテジー2008

    • Author(s)
      小野寺伸
    • Organizer
      「β1, 3グルカンと核酸医薬DDSおよび免疫学との接点」第1回研究会
    • Place of Presentation
      札幌市、北海道情報大学札幌サテライト
    • Year and Date
      2008-07-22
    • Related Report
      2008 Annual Research Report
  • [Presentation] Establishment of a novel antisense-oligonucleotide therapy using a natural DNA carrier molecule and its effectiveness on murine model of arthritis2008

    • Author(s)
      Onodera S
    • Organizer
      International Symposium on"Nanotoxicology Assessm ent and Biomedical, Environmental Applicationof F ifle Particles and Nanotubes"
    • Place of Presentation
      札幌市、学術交流会館
    • Year and Date
      2008-06-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] チタン磨耗粉によって惹起されるオステオライシス発生機序におけるMIF(マクロファージ遊走阻止因子)の機能解析2007

    • Author(s)
      小野寺 伸
    • Organizer
      平成19年度厚生労働科学研究費補助金 化学物質リスク研究事業「ナノ微粒子体内動態可視化法の開発」第3回研究成果発表会
    • Place of Presentation
      登別市 第一滝本館
    • Year and Date
      2007-11-12
    • Related Report
      2007 Annual Research Report
  • [Presentation] 卵巣摘出後骨粗鬆症に対するMIF-DNAワクチンの効果2007

    • Author(s)
      小野寺 伸
    • Organizer
      第22回日本整形外科学会基礎学術集会 シンポジウム
    • Place of Presentation
      浜松市
    • Year and Date
      2007-10-25
    • Related Report
      2008 Final Research Report
  • [Presentation] 卵巣摘出後骨粗鬆症に対するMIF-DNAワクチンの効果2007

    • Author(s)
      小野寺 伸
    • Organizer
      第22回 日本整形外科学会基礎学術集会 シンポジウム
    • Place of Presentation
      浜松市 アクトシティ浜松
    • Year and Date
      2007-10-25
    • Related Report
      2007 Annual Research Report
  • [Presentation] マウス卵巣摘出骨粗鬆症に対するMIF-DNAワクチンを用いた新規能動的抗体療法2007

    • Author(s)
      小野寺 伸
    • Organizer
      第7回北海道整形外科 オステオポローシスセミナー
    • Place of Presentation
      札幌市
    • Year and Date
      2007-06-30
    • Related Report
      2008 Final Research Report
  • [Presentation] マウス卵巣摘出骨粗鬆症に対する MIF-DNA ワクチンを用いた新規能動的抗体療法2007

    • Author(s)
      小野寺 伸
    • Organizer
      第7回 北海道整形外科 オステオポローシスセミナー
    • Place of Presentation
      札幌市札幌プリンスホテル
    • Year and Date
      2007-06-30
    • Related Report
      2007 Annual Research Report
  • [Presentation] A NOVEL THERAPEUTIC DNA VACCINE TARGETING MACROPHAGE MIGRATION INHIBITORY FACTOR PROTECTS JOINTS AGAINST INFLAMMATION AND DESTRUCTION IN MURINE MODELS OF ARTHRITIS2007

    • Author(s)
      Onodera S
    • Organizer
      AMERICAN SOCIEY OF GENE THERAPY 10TH ANNUAL MEETING
    • Place of Presentation
      Seattle, USA
    • Year and Date
      2007-06-01
    • Related Report
      2008 Final Research Report
  • [Presentation] A NOVEL THERAPEUTIC DNA VACCINE TARGETING MACROPHAGE MIGRATION INHIBITORY FACTOR PROTECTS JOINTS AGAINST INFLAMMATION AND DESTRUCTION IN MURINE MODELS OF ARTHRITIS2007

    • Author(s)
      Onodera S
    • Organizer
      AMERICAN SOCIEY OF GENE THERAPY 10TH ANNUAL MEETING
    • Place of Presentation
      Washington State Convention and Trade Center, SEATTLE, USA
    • Year and Date
      2007-06-01
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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