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Lookup NU author(s): Dr Emma Barksby, Ilka Wappler, Dr Heiko Peters, Dr Jenny Milner, Emeritus Professor Tim Cawston, Emeritus Professor Drew Rowan
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Objective. To identify the genes up-regulated by interleukin-1 (IL-1) in combination with oncostatin M (OSM) in chondrocytes that may be involved in mechanisms of cartilage repair and degradation. Methods. Gene microarray and real-time polymerase chain reaction (PCR) experiments were performed using RNA from SW1353 chondrocytes and primary human articular chondrocytes. Sections prepared from murine joints, injected with adenovirus vectors overexpressing IL-1 and/or OSM, were analyzed by immunohistochemistry for selected proteins. Results. The combination of IL-1. and OSM markedly up-regulated the expression of various genes, including matrix metalloproteinases (MMPs), cytokines, chemokines, extracellular matrix components, and genes involved in signal transduction. Real-time PCR confirmed a synergistic induction of several MMPs, activin A, pentraxin 3 (PTX-3), and IL-8. The in vivo findings further indicated that stimulation with IL-1 plus OSM induced protein expression of activin A, PTX-3, and KC (the murine homolog of IL-8), as compared with the changes induced by individual cytokine treatment and unstimulated controls. Conclusion. The results confirm that the potent proinflammatory cytokine combination of IL-1. plus OSM synergistically and coordinately up-regulates many genes and several MMPs. Moreover, chondrocytes exhibit a potential repair response following this procatabolic stimulus such that the repair mechanisms are ultimately overwhelmed by degradative processes in the cartilage. This gene-profiling study provides insight into the complex processes that mediate joint disease in the inflammatory arthritides through the coordinated expression of multiple genes.
Author(s): Barksby HE, Hui W, Wappler I, Peters HH, Milner JM, Richards CD, Cawston TE, Rowan AD
Publication type: Article
Publication status: Published
Journal: Arthritis & Rheumatism
Year: 2006
Volume: 54
Issue: 2
Pages: 540-550
ISSN (print): 0004-3591
ISSN (electronic): 1529-0131
Publisher: John Wiley & Sons, Inc.
URL: http://dx.doi.org/10.1002/art.21574
DOI: 10.1002/art.21574
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