Interleukin‐1 in combination with oncostatin M up‐regulates multiple genes in chondrocytes: Implications for cartilage destruction and repair
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AbstractObjectiveTo 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.MethodsGene 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.ResultsThe 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.ConclusionThe 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.
