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Effects of Hyperlipidemia on Progression of Knee Osteoarthritis

Research Project

Project/Area Number 17591602
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

AKAGI Masao  Kinki University, School of Med., Associate Professor (00273441)

Co-Investigator(Kenkyū-buntansha) ASADA Shigeki  Kinki University, School of Med., Lecturer (00330283)
森 成志  近畿大学, 医学部, 助手 (80351584)
西村 俊司  近畿大学, 医学部附属病院, 助手 (80388545)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,790,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥90,000)
Fiscal Year 2007: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2006: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2005: ¥2,900,000 (Direct Cost: ¥2,900,000)
KeywordsKnee Osteoarthritis / Cartilage degeneration / Oxidized LDL / Lectine-like oxidized lipoproteinreceptor-1(LOX-1) / Hyperlipidemia / Life-style related disease / Basic fibroblast growth factor / 実験的変形性関節症 / LOX-1
Research Abstract

【Purpose】 Recently, it has been demonstrated in in-vivo and vitro studies that lectin-like oxidized low-density lipoprotein LDL (ox-LDL) receptor-1 (LOX-1) expresses on articular chondrocytes and suggested that its ligand ox-LDL plays some roles in degeneration of articular cartilage. The purpose of this study is to examine effects of hyperlipidemic loading on articular cartilage degeneration using a congenital hyperlipidemic rabbit (KHC).
【Methods】 Japanese white rabbits (JW, n=6) and KHC rabbits (n=6) underwent transection of the anterior cruciate ligament and excision of the medial meniscus in the right knee. Sham operation was performed in the left knee. All animals were killed at 8 weeks following the surgery. The weight-bearing areas of the medial femoral condyle were subjected to histological evaluation according to the modified Mankin scoring system. Furthermore, these were subjected to LOX-1, ox-LDL and basic fibroblast growth factor (bFGF) immunohistochemical staining. To exam … More ine effect of ox-LDL on bFGF expression in chondrocytes rabbit articular chondrocytes (RACs) were stimulated with ox-LDL (0, 50, 100 μg/m1) and bFGF mRNA expression was investigated with RT-PCR. To know whether the effect is mediated by LOX-1, cells were pre-incubated with anti-human LOX-1 antibody (JTX92, 50 μg/m1), and then stimulated with ox-LDL at various concentrations.
【Results】 Mean Mankin score in the right knee of the KHC rabbits was significantly larger than that of JW rabbits (23.0±1.8 and 15.2±4.8, respectively, p < 0.01). Mean Mankin score in the left knee (Sham op. side) of the KHC rabbits was also significantly larger than that of JW rabbits (6.5±1.4 and 2.5±2.0, respectively, p<0.05). Presence of ox-LDL and expression of LOX-1 were noted in the right knee cartilage of both rabbits. However, immunoreactivity of ox-LDL was stronger in the left knee of KHC rabbits than in that of JW rabbits. Immunoreactivity of bFGF in both right and left knee cartilages was significantly less in the KHW rabbits than in JW rabbits. In rabbit chondrocyte culture, ox-LDL significantly reduced bFGF mRNA expression in a dose dependent manner, and pretreatment with anti-LOX-1 monoclonal antibody (JTX92) significantly reversed this reduction.
【Conclusion】 These observations support the hypothesis that hyperlipidemia may be one of risk factors for osteoarthritis and suggest that the ox-LDL/LOX-1 system may be involved. Reduction of bFGF expression in chondrocytes due to the system may cause the acceleration of cartilage degeneration. Less

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (21 results)

All 2007 2006 2005

All Journal Article (11 results) (of which Peer Reviewed: 5 results) Presentation (10 results)

  • [Journal Article] Possible Involvement of Oxidized Low-density Lipoprotein with Lectin-like Oxidized Low-density Lipoprotein Receptor 1 in Pathogenesis and Progression of Human Osteorthritis2007

    • Author(s)
      Masao Akagi, et. al.
    • Journal Title

      Osteoarthritis and Cartilage 15(3)

      Pages: 281-290

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Possible Involvement of Oxidized Low-density Lipoprotein with Lectin-like Oxidized Low-density Lipoprotein Receptor 1 in Pathogenesis and Progression of Human Osteoarthritis.2007

    • Author(s)
      Masao Akagi, Soya Kanata, Shigeshi Mori, Hiroyuki Itabe, Tatsuya Sawamura, Chiaki Hamanishi
    • Journal Title

      Osteoarthritis and Cartilage 15(3)

      Pages: 281-290

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Possible Involvement of Oxidized Low-density Lipoprotein with.Lectin-like Oxidized Low-density Lipoprotein Receptor 1 in Pathogenesis and Progression of Human Osteoarthritis2007

    • Author(s)
      Masao Akagi
    • Journal Title

      Osteoarthritis and Cartilage 15(3)

      Pages: 281-290

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cyclic Tensile Stretch Load and Oxidized Low Density Lipoprotein Synergistically Induce Lectin-like Oxidized LDL Receptor-1 in Cultured Bovine Chondrocytes,Resulting in Decreased Cell Viability and Glycosaminoglycan Synthesis2006

    • Author(s)
      Masao Akagi
    • Journal Title

      J Orthop.Res 24(8)

      Pages: 1782-1790

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Oxidized LDL binding to LOX-1 upregulates VEGF expression in cultured bovine chondrocytes through activation of PPAR-γ2006

    • Author(s)
      Sohya Kanata
    • Journal Title

      Biochemistry and Biophysiology Research Communication 348(3)

      Pages: 1003-1010

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Cyclic Tensile Stretch Load and Oxidized Low Density Lipoprotein Synergistically Induce Lectin-like Oxidized LDL Receptor-1 in Cultured Bovine Chondrocytes, Resulting in Decreased Cell Viability and Glycosaminoglycan Synthesis.2006

    • Author(s)
      Masao Akagi, Shunji Nishimura, Kohji Yoshida, Takumi Kakinuma, Tatsuya Sawamura, Hiroshi Munakata, Chiaki Hamanishi.
    • Journal Title

      J Orthop. Res 24(8)

      Pages: 1782-1790

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Oxidized LDL binding to LOX-1 upregulates VEGF expression in cultured bovine chondrocytes through activation of PPAR-γ.2006

    • Author(s)
      Sohya Kanata, Masao Akagi, Shunji Nishimura, Sumio Hayakawa, Kohji Yoshida, Tatsuya Sawamura, Hiroshi Munakata, Chiaki Hamanishi
    • Journal Title

      Biochem Biophy Res Comm 348(3)

      Pages: 1003-1010

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Cyclic Tensile Stretch Load and Oxidized Low Density Lipoprotein Synergistically Induce Lectin-like Oxidized LDL Receptor-1 in Cultured Bovine Chondrocytes, Resulting in Decreased Cell Viability and Glycosaminoglycan Synthesis.2006

    • Author(s)
      Masao Akagi, et al.
    • Journal Title

      J Orthop. Res, 24(8)

      Pages: 1782-1790

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Oxidized LDL binding to LOX-1 upregulates VEGF expression in cultured bovine chondrocytes through activation of PPAR-g.2006

    • Author(s)
      Sohya Kanata, et al.
    • Journal Title

      Biochemistry and Biophysiology Research Communication 348(3)

      Pages: 1003-1010

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 脂血症負荷が膝関節軟骨変性におよぼす影響:自然発症高脂血症ウサギ(KHC)を用いた実験的研究2005

    • Author(s)
      西村 章朗
    • Journal Title

      近畿大医誌 30(3,4)

      Pages: 93-103

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Effects of Hyperlipidemia on Progression of Knee Osteoarthritis2005

    • Author(s)
      Akio Nishimura, Masao Akagi, Chiaki Hamanishi
    • Journal Title

      Med J of Kinki University 30(3,4)

      Pages: 93-103

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] OXIDIZED LOW-DENSITY LIPOPROTEIN BINDING TO LECTIN-LIKE OX-LDL RECEPTOR-1 UPREGULATES VASCULAR ENDOTHERIAL GROWTH FACTOR EXPRESSION IN CULTURED BOVINE ARTICULAR CHONDROCYTES THROUGH PPAR-GAMMA ACTIVATION2007

    • Author(s)
      Sohya Kanata
    • Organizer
      53nd Annual Meeting of the Orthopaedic Research Society
    • Place of Presentation
      San Diego,CA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Oxidized low-density lipoprotein binding to lectin-like oxidized lipoprotein receptor-1(LOX-1) upregulates Vascular endothelial growth factor expression in cultured bovine articular chondrocytes through PPAR-gamma activation2007

    • Author(s)
      Sohya Kanata, Masao Akagi, Shunji Nishimura, Akio Nishimura, Shigeki Asada, Shigeshi Mori, Chiaki Hamanishi
    • Organizer
      53nd Annual Meeting of the Orthopaedic Research Society
    • Place of Presentation
      San Diego, CA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 高脂血症負荷が膝関節軟骨変性におよぼす影響:自然発症高脂血症ウサギ(KHC)を用いた実験的研究2006

    • Author(s)
      西村 章朗
    • Organizer
      第19回日本軟骨代謝学会
    • Place of Presentation
      横浜
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 牛培養軟骨細胞における酸化LDL/LOX-1結合はVEGF発現を亢進する.PPAR-gammaの関与2006

    • Author(s)
      金田 宗也
    • Organizer
      第19回日本軟骨代謝学会
    • Place of Presentation
      横浜
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The effects of hyperlipidemic loading on cartilage degeneration in the knee : Experimental studies using a congenital hyperlipidemic rabbit(KHC rabbit)2006

    • Author(s)
      Akio Nishimura, Masao Akagi, Sohya Kanata Shigeshi Mori, Shigeki Asada, Chiaki Hamanishi
    • Organizer
      19th Annual Meeting of the Japanese Society of Cartilage Metabolism
    • Place of Presentation
      Yokohama
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Oxidized-LDL binding to Lectin-like ox-LDL receptor 1(LOX-1) in bovine cultured chondrocytes increases VEGF expression through activation of PPAR-gamma.2006

    • Author(s)
      Sohya Kanata, Masao Akagi, Akio Nishimura, Shigeshi Mori, Shigeki Asada, Chiaki Hamanishi
    • Organizer
      19th Annual Meeting of the Japanese Society of Cartilage Metabolism
    • Place of Presentation
      Yokohama
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 高脂血症の変形性籐関節症に与える影響2005

    • Author(s)
      西村 章朗
    • Organizer
      第20回日本整形外科学会基礎学術集会
    • Place of Presentation
      伊勢
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 牛培養軟骨細胞における酸化LDL/LOX-1結合はVEGF発現及びMMP発現を亢進する2005

    • Author(s)
      金田 宗也
    • Organizer
      第20回日本整形外科学会基礎学術集会
    • Place of Presentation
      伊勢
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] PRESENCE OF OXIDIZED LOW DENSITY LIPOPROTEIN(OX-LDL)WITH LECTIN-LIKE OXIDIZED LOW DENSITY LIPOPROTEIN RECEPTOR-1(LOX-1)CORRELATES TO DEGENERATION OF HUMAN OSTEOARTHRITIC CARTILAGE2005

    • Author(s)
      Masao Akagi, et. al.
    • Organizer
      10th World Congress of Osteoarthritis Research Society International
    • Place of Presentation
      Boston,Massachusetts,USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Presence of oxidized low density lipoprotein(ox-LDL) with lectin-like oxidized lipoprotein receptor-1(LOX-1) correlates to degeneration of human osteoarthritic cartilage.2005

    • Author(s)
      Masao Akagi, Muneya Kanata, Akio Nishimura, Shigeshi Mori, Shunji Nishimura, Chiaki Hamanishi.
    • Organizer
      10th World Congress of Osteoarthritis Research Society International
    • Place of Presentation
      Boston, MA, USA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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