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MR Vol.14 No.1 indexに戻る
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MODERN RHEUMATOLOGY
Vol.14 No.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 |
| 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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