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A trial of cartilage repair of injured articular cartilage in osteoarthritis joints by exogenous growth factors

Research Project

Project/Area Number 04454377
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Orthopaedic surgery
Research InstitutionKyushu University

Principal Investigator

JINGUSHI Seiya  Kyushu University Faculty of Medicine, Assistant Professor, 医学部, 助手 (80235829)

Co-Investigator(Kenkyū-buntansha) IZUMI Toshihiro  Kyushu University Faculty of Medicine, Assistant Professor, 医学部, 助手 (90253426)
HOTOKEBUCHI Takao  Kyushu University Faculty of Medicine, Assistant Professor, 医学部, 助手 (40190219)
宮原 寿明  九州大学, 医学部, 助手 (10209934)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1993: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1992: ¥3,200,000 (Direct Cost: ¥3,200,000)
Keywordsarticular cartilage / growth factors / osteoarthritis / 関節軟骨 / 成長因子 / 変形性関節症 / 軟骨修復 / 軟骨細胞 / 軟骨病態マーカー / 軟骨 / 関節液
Research Abstract

The following series of experiments were carried out.
1) Expression of growth factors in various cartilage tissues : Expression of transforming growth factor beta (TGFbeta) and fibroblast growth factors (FGFs) were examined in rat epiphysis. All the growth factors were expressed in the proliferating chondrocytes. TGFbeta was also localized in the matrix around the hypertrophic chondrocytes. Additionally, rat rib cartilage was investigated. Growth hormone induced expression of TGFbeta and insulin-like growth factor in the chondrocytes. In rat fracture calluses, many growth factors including FGFs and TGFbeta were expressed in the cartilage tissue. These experiments showed that various growth factors were expressed in the cartilage tissues suggesting that the growth factors regulate cell proliferation or differentiation in cartilage formation.
2) Cartilage metabolic markers in joint fluids from hips with osteonecrosis of the femoral head :
Significant increases in all markers including aggre … More can, typeII procollagen, stromelysin and tissue inhibitor of metalloproteinases were noted in the earliest stage of the disease, only a few months after onset of symptoms. These molecular marker data suggest that the turnover rates of both major matrix components in hip joint cartilage (aggrecan and type II collagen) are greatly increased following osteonecrosis of the femoral head. These markers might be used for monitoring cartilage repair by growth factors.
3) In vivo effects of growth factors on normal animal joints :
Basic fibroblast growth factors (bFGF) was selected as a growth factor for this experiment. Effects of exogenous bFGF on normal articlar cartilage of young rat knee joint or adult mouse knee joint were investigated. In a young rat kneejoint, bFGF injection caused to stimulate artiuclar cartilae developement. In a adult mouse knee joint, proliferative reaction including synovial hyperplasia and osteophyte formation were observed. In both of the two experiments, bFGF seemed to stimulate progenitors of chondrocytes or immature chondrocytes to proliferate resulting in a new cartilage formation.
4) In vivo effects of exogenous growth factors on injured articular cartilage of animal joints : Effects of exogenous bFGF with perichondrium graft onfull-thickness articular cartilage defectof rabbit knee joint were investigated. Six months after operation, the defect was covered with good cartilage tissue. Additionally, proliferative reaction including synovial hyperplasia and osteophyte formation were observed in the joint. In order to prevent such additional reaction, an appropriate carrier will be necessary. The carrier also will enable to release growth factors at an appropriate dose for a long time in the joint. Less

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] 神宮司誠也: "骨折治癒過程での軟骨形成におけるaFGFの役割" 日本骨代謝学会雑誌. 10. 193-198 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 杉岡洋一、神宮司誠也他: "特発性大腿骨頭壊死症における関節軟骨病変について-股関節液中の総Glycosaminoglycan濃度と摘出骨頭標本の組織学的検討-" 厚生省特定疾患特発性大腿骨頭壊死症調査研究班平成3年度研究報告書. 51-53 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 神宮司誠也、岩城彰他: "Basic Fibrobalst Growth Factor及びTransforming Growth Factor betaの骨折治癒過程における細胞増殖抑制への関与" 骨折. 16-1. 5-8 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 神宮司誠也、杉岡洋一他: "特発性大腿骨頭壊死症における関節液内軟骨基質分解酵素(stromelysin)について" Hip Joint. 20. 217-219 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 杉岡洋一、佛淵孝夫、神宮司誠也他: "特発性大腿骨頭壊死症における関節液内軟骨基質分解酵素(stromelysin)について" 厚生省特定疾患特発性大腿骨頭壊死症調査研究班平成5年度研究報告書. 15-16 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 神宮司誠也: "関節炎とその病態マーカー、II型コラーゲンCプロペプチド" 炎症と免疫. 2. 70-74 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Jingushi S, Scylly S P, et al.: "Transforming Growth Factor β1 and Fibrobalst Growth Factors in Rat Growth Plate" J Orthop Res. 13巻. 761-768 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Izumi T, Shida J, Jingushi S, et al.: "Administration of growth hormone modulates the gene expression of basic fibroblast growth factor in rat costal cartilage, toth in vivo and in vitro" Mol Cell Endocrinol. 112巻. 95-99 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shida J, Jingushi S, et al.: "Basic Fibroblast Growth Factor Stimulates Articular Cartilage Enlargement in Young Rats In Vivo." J Orthop Res. 14. 265-272 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 神宮司誠也、杉岡洋一他: "関節マーカー(大腿骨頭壊死股関節液における軟骨病態マーカー)" 岩田久、新名正由編:メディカル レビュー社、東京, 7 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Jingushi S: "A role of aFGF for cartilage formation in rat fracture repair." Journal of Japanese Society of Bone and Mineral Society. 10 (2). 193-198 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sugioka Y,Jingushi S,Saikawa I,Hotokebuchi T,Miyahara H,Hirano K,Tsutsui H,Lohmander LS: "Articular cartilage in the hip of idiopathic osteonecrosis of the femoral head." Investigation Committee Report on the Idiopathic Osteonecrosis of the Femoral Head. 51-53 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Jingushi S,Iwaki A,Izumi T,Shida J,Sugioka Y,Bolander M: "Expression of basic fibroblast growth factor and transforming growth factor beta and cell proliferation in rat fracture repair." Bone. 16 (1). 5-8 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Jingushi S,Sugioka Y,Hotokebuchi T,Tsutsui H,Lohmander LS,Hoerner LA,Lark MW: "Stromelysin in the hip joint fluids of idiopathic osteonecrosis of the femoral head." Hip Joint. 20. 217-219 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sugioka Y,Hotokebuchi T,Jingushi S,Tsutsui H,Lohmander LS,Hoerner LA,Lark MW: "Stromelysin in the hip joint fluids of idiopathic osteonecrosis of the femoral head." Investigation Committee Report on the Idiopathic Osteonecrosis of the Femoral Head. 15-16 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Jingushi S: "Arthritis and metabolic markers-C-propeptide of type II collagen" Inflammation and Immunology. 2 (2). 70-74 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Jingushi S,Scully S P,Joyce M E,Sugioka Y,Bolander M E: "Transforming Growth Factor beta1 and Fibroblast Growth Factors in Rat Growth Plate." J Orthop Res. 13 (5). 761-768 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Izumi T,Shida J,Jingushi S,Hotokebuchi T,Sugioka Y: "Administration of growth hormone modulates the gene expression of basic fibroblast growth factor in rat costal cartilage, both in vivo and in vitro." Molecular and Cellular Endocrinology. 112. 95-99 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shida J,Jingushi S,Izumi T,Iwaki A,Sugioka Y.: "Basic Fibroblast Growth Factor Stimulates Articular Cartilage Enlargement in Young Rats In Vivo." J Orthop Res. 14 (2). 265-272 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Jingushi,S: "Transforming grwoth factor beta 1 and fibroblast growth factors in rat growh plate" Journal of Orthopaedic Research. (in print). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Jingushi,S: "A combination treatment with basic flbroblast growth factor for a full-thickness articular cartilage defect" Orthopaedic Transaction. (in print). (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shida,J: "A single injection of basic FGF stimulates articular cartilage enlargement in rat knee joints" Orthopaedic Transaction. (in print). (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Izumin,T: "Growth hormone modulated the gene expression of growth factors in rat costal cartilage in vivo" Orthopaedic Transaction. (in print). (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Jingushi,S: "Martkers of cartilage matrix turnover in joint fluids from hips with the osteonecrosis of the femoral head" Orthopaedic Transaction. (in print). (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 神宮司誠也: "関節炎とその病態マーカー:II型コラーゲンCプロペプチド" 炎症と免疫. 2. 70-74 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Jingushi,S: "Markers of cartilage matrix turnover in joint fluids from hips with the osteonecrosis of the femoral head" Orthopaedic Transactions. (in print). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Jingushi,S: "A combination treatment with basic fibroblast growth factor and perichondrium autograft for a full‐thickness articular cartilage defect" Orthopaedic Transactions. (in print). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Izumi,T: "Growth hormone modulated the gene expression of growth factors in rat costal cartilage in vivo" Orthopaedic Transactions. (in print). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Shida,J: "A single injection of basic fibroblast growth factor stimulates articular cartilage enlargement in rat knee joints" Orthopaedic Transactions. (in print). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 神宮司 誠也: "特発性大腿骨頭壊死症における関節軟骨病変についてー股関節液中のC(II)-propeptide濃度ー" 日本整形外科学会雑誌. 66. S581- (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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