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MODERN RHEUMATOLOGY Vol.14 No.1
>MR14-1
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Requirement of mitogen-activated protein kinase for collagenase production by the fibronectin fragment in human articular chondrocytes in culture
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| Tadashi Yasuda1 , Sohel M. Julovi1, Teruko Hiramitsu1, Makoto Yoshida1 and Takashi Nakamura1 |
| (1) Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan |
Received: 14 May 2003 Accepted: 07 August 2003 |
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Abstract |
| Abstract Fibronectin fragments have been shown to up-regulate matrix metalloproteinase production in chondrocytes. We investigated the roles of mitogen-activated protein kinase (MAPK) pathways activated by the COOH-terminal heparin-binding fibronectin fragment (HBFN-f) in collagenase production by human chondrocytes in culture. In articular cartilage explant culture, HBFN-f stimulated type II collagen cleavage by collagenase in association with increased secretion of MMP-1 and MMP-13. In human articular chondrocytes, HBFN-f induced the collagenases with activation of the extracellular signal-regulated kinase (ERK), p38, and the c-Jun NH2-terminal kinase (JNK). PD98059 that inhibits the ERK pathway blocked HBFN-f-stimulated production of MMP-1 and MMP-13 in explant culture. SB203580 at 1μM, the concentration that inhibits p38 only, partially suppressed HBFN-f-induced collagenase production, whereas at 10μM, the inhibitor that blocks both p38 and JNK almost completely inhibited collagenase induction. PD98059 and SB203580 individually blocked HBFN-f-increased cleavage of type II collagen in the explant culture, although 10μM SB203580 strongly inhibited the collagen cleavage compared with 1μM of the inhibitor. These results indicate that collagenase production leading to type II collagen cleavage in cartilage explants requires ERK, p38, and JNK. |
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| Key words |
| Key words Chondrocyte - Collagenase - Fibronectin fragment - Mitogen-activated protein kinase (MAPK) - Type II collagen |
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