このエントリーをはてなブックマークに追加
ID 32943
FullText URL
Author
Demircan, Kadir
Hatipoglu, Omer F.
Apte, Suneel S.
Abstract

Objective
To compare induction of the aggrecanases (ADAMTS-1, ADAMTS-4, ADAMTS-5, ADAMTS-8, ADAMTS-9, and ADAMTS-15) by interleukin-1 (IL-1) and tumor necrosis factor (TNF) in chondrocyte-like OUMS-27 cells and human chondrocytes, and to determine the mechanism of induction of the most responsive aggrecanase gene.

Methods
OUMS-27 cells were stimulated for different periods of time and with various concentrations of IL-1 and/or TNF. Human chondrocytes obtained from osteoarthritic joints and human skin fibroblasts were also stimulated with IL-1 and/or TNF. Total RNA was extracted, reverse transcribed, and analyzed by quantitative real-time polymerase chain reaction and Northern blotting. ADAMTS-9 protein was examined by Western blotting, and the role of the MAPK signaling pathway for ADAMTS9 induction in IL-1-stimulated OUMS-27 cells was investigated.

Results IL-1 increased messenger RNA (mRNA) levels of ADAMTS4, ADAMTS5, and ADAMTS9 but not ADAMTS1 and ADAMTS8. The fold increase for ADAMTS9 mRNA was greater than that for mRNA of the other aggrecanase genes. The increase of ADAMTS9 mRNA by IL-1 stimulation was greater in chondrocytes than in fibroblasts. The combination of IL-1 and TNF had a synergistic effect, resulting in a considerable elevation in the level of ADAMTS9 mRNA. ADAMTS-9 protein was also induced in IL-1-stimulated OUMS-27 cells. The MAPK inhibitors SB203580 and PD98059 decreased ADAMTS9 up-regulation in OUMS-27 cells.

Conclusion
ADAMTS9 is an IL-1- and TNF-inducible gene that appears to be more responsive to these proinflammatory cytokines than are other aggrecanase genes. Furthermore, these cytokines had a synergistic effect on ADAMTS9. Together with the known ability of ADAMTS-9 to proteolytically degrade aggrecan and its potential to cleave other cartilage molecules, the data suggest that ADAMTS-9 may have a pathologic role in arthritis.

Keywords
ADAMTS
aggrecanase
arthritis
chondrocyte
metalloproteinases
IL-1
Note
Digital Object Identifier: 10.1002/art.21010
Published with permission from the copyright holder. This is the author's copy, as published in Arthritis & Rheumatism, 5 May 2005, Volume 52, Issue 5, Pages 1451-1460.
Publisher URL: http://dx.doi.org/10.1002/art.21010
Direct access to Thomson Web of Science record
Copyright © 2005 by the American College of Rheumatology. All rights reserved.
Published Date
2005-5
Publication Title
Arthritis & Rheumatism
Volume
volume52
Issue
issue5
Publisher
American College of Rheumatology
Start Page
1451
End Page
1460
ISSN
0004-3591
NCID
AA00551881
Content Type
Journal Article
language
英語
Copyright Holders
American College of Rheumatology
File Version
author
Refereed
True
DOI
Web of Sience KeyUT
Submission Path
internal_medicine/5