Tools
Tools
Koshy, P. J. T., Lundy, C. J., Rowan, A. D., Porter, S., Edwards, D. R. 
ORCID: https://orcid.org/0000-0002-3292-2064, Hogan, A., Clark, I. M. and Cawston, T. E.
(2002)
The modulation of matrix metalloproteinase and ADAM gene expression in human chondrocytes by interleukin-1 and oncostatin M: A time-course study using real-time quantitative reverse transcription–polymerase chain reaction.
Arthritis and Rheumatism, 46 (4).
pp. 961-967.
ISSN 1529-0131
Abstract
Objective: Previous studies have reported elevated levels of interleukin-1 (IL-1) and oncostatin M (OSM) in rheumatoid joints, as well as the synergistic degradation of human articular cartilage by this cytokine combination. The present study was undertaken to investigate the ability of IL-1 and OSM to modulate gene expression of matrix metalloproteinase (MMP), ADAM, and ADAM-TS (ADAM with thrombospondin motifs) family members in human chondrocytes. Methods: T/C28a4 human chondrocytes were stimulated for 2–48 hours with IL-1 and/or OSM. Total RNA was harvested, reverse transcribed, and assessed by real-time polymerase chain reaction for the expression of various MMP, ADAM, and ADAM-TS messenger RNAs (mRNA). Results were normalized to 18S ribosomal RNA. Results: IL-1 and OSM synergized to markedly induce the expression of the collagenases MMP-1, MMP-8, and MMP-13 as well as MMP-3, an activator of proMMPs. Expression of mRNA for MMPs 1, 3, and 13 was induced early, whereas that of MMP-8 mRNA occurred late. Gene expression of MMP-14, an MMP that degrades collagen and activates proMMP-13, was elevated by this combination. IL-1 and OSM also synergized to induce gene expression of the aggrecanase ADAM-TS4, but not ADAM-TS5. Conclusion: These data indicate that the potent cartilage-degrading properties of the combination of IL-1 and OSM are potentially mediated by a synergistic induction of the aggrecan-degrading enzyme ADAM-TS4 and the collagen-degrading enzymes MMP-1, MMP-8, MMP-13, and MMP-14, although differences in the magnitude of response and in the time course of induction were observed. A role for MMPs 3 and 14 in the activation of proMMPs may also be implicated.
| Item Type: | Article |
|---|---|
| Additional Information: | Research Funding: Arthritis Research Campaign; Medical Research Council of Great Britain |
| Faculty \ School: | Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine Faculty of Medicine and Health Sciences > Research Groups > Musculoskeletal Medicine |
| Depositing User: | EPrints Services |
| Date Deposited: | 01 Oct 2010 13:36 |
| Last Modified: | 24 Sep 2024 10:18 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/398 |
| DOI: | 10.1002/art.10212 |
Actions (login required)
 |
View Item |