Inhibiton of Thrombin-induced Cartilage Proteoglycan Release by Argatroban
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概要
- 論文の詳細を見る
Deposition of fibrin in synovial tissue is a prominent feature of rheumatoid arthritis (RA). We previously reported high levels of thrombin-antithrombin III complex in RA synovial fluids. These findings strongly suggest local synthesis of thrombin in RA joints. In order to study the possible role of thrombin in cartilage destruction in RA, we examined the effect of thrombin on cartilage proteoglycan (PG) degradation in cultured bovine articular cartilage. Thrombin induced PG release into the medium in a concentration- and time-dependent manner, as reported previously (Furmaniak-Kazmierczak E et al: J Clin Invest 94: 472-480, 1994). Since heat pre-treatment of the cartilage did not affect this effect and the thrombin-induced loss of proteoglycan was uniform within the cartilage as revealed by toluidine blue staining, the degradation mechanism did not appear to require chondrocytes. A synthetic thrombin-specific inhibitor, argatroban ((2R, 4R)-4-methy-1-(N2-((3-methy-1,2,3,4-tetrahydro-8-quinolinyl) sulfonyl)-L-arginyl)-2-piperidinecarboxylic acid) at 1μM was shown to inhibit 1OOu/ml thrombin-induced cartilage degradation by half. Almost complete inhibition was obtained at 10 μM. These results implicate that thrombin may play a role in cartilage degradation in RA and may provide a new approach in the treatment of RA.
- 神戸大学の論文
- 1996-01-31
著者
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Fujita Ikuo
Department Of Orthopaedic Surgery Hyogo Medical Center For Adults
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MIZUNO Kosaku
Department of Orthopaedic Surgery, Kobe University School of Medicine
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Fujita Ikuo
Department Of Orthopedic Surgery Kobe University School Of Medicine
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Fujita Ikuo
Department Of Oral Anatomy Asahi University School Of Dentistry
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Hirata Soichiro
Faculty of Health Science, Kobe University School of Medicine
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Hijikata-Okunomiya Akiko
Faculty of Health Science, Kobe University School of Medicine
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Ishikawa Hitoshi
Faculty of Health Science, Kobe University School of Medicine
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Saura Ryuichi
Department of Orthopaedic Surgery, Kobe University School of Medicine
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Okamoto Shosuke
Kobe Research Projects on Thrombosis and Haemostasis
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Hirata Soichiro
Faculty Of Health Sciences Kobe University School Of Medicine
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Hirata Soichiro
Faculty Of Health Science Kobe University School Of Medicine
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Ishikawa Hitoshi
Faculty Of Health Sciences Kobe University School Of Medicine
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Hijikata-okunomiya Akiko
Faculty Of Health Science Kobe University School Of Medicine
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Ishikawa Hitoshi
Faculty Of Health Science Kobe University School Of Medicine
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Mizuno K
Department Of Orthopedic Surgery Kobe University Graduate School Of Medicine
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Mizuno Kosaku
Department Of Orthopaedic Surgery Kobe University School Of Medicine
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Saura Ryuichi
Department Of Orthopaedic Surgery Kobe University School Of Medicine
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Saura Ryuuichi
Faculty Of Health Science Kobe University School Of Medicine
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Saura Ryuichi
Kobe University School Of Medicine
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Hirata Souichirou
Faculty Of Health Science Kobe University School Of Medicine
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Ishikawa Hitoshi
Faculty Of Health Science Kobe University
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