Published online before print July 19, 2007

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Copyright © 2007 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2007.061083

Accepted for publication May 25, 2007.

Article

Activation of Interleukin-1 Signaling Cascades in Normal and Osteoarthritic Articular Cartilage

Zhiyong Fan^*, Stephan Söder, Stephan Oehler, Katrin Fundel, and Thomas Aigner^@

From the Department of Pathology,* University of Erlangen, Erlangen; the Institute of Pathology, University of Leipzig, Leipzig; the Orthopedic Hospital, Rummelsberg, Schwarzenbruck; and the Institute for Informatics, Ludwig-Maximilians-Universität München, München, Germany

^@ To whom correspondence should be addressed. E-mail: thomas.aigner{at}medizin.uni-leipzig.de.

	Abstract

Interleukin (IL)-1 is one of the most important catabolic cytokines in rheumatoid arthritis. In this study, we were interested in whether we could identify IL-1 expression and activity within normal and osteoarthritic cartilage. mRNA expression of IL-1 and of one of its major target genes, IL-6, was observed at very low levels in normal cartilage, whereas only a minor up-regulation of these cytokines was noted in osteoarthritic cartilage, suggesting that IL-1 signaling is not a major event in osteoarthritis. However, immunolocalization of central mediators involved in IL-1 signaling pathways [38-kd protein kinases, phospho (P)-38-kd protein kinases, extracellular signal-regulated kinase 1/2, P-extracellular signal-regulated kinase 1/2, c-Jun NH₂-terminal kinase 1/2, P-c-Jun NH₂-terminal kinase 1/2, and nuclear factor B] showed that the four IL-1 signaling cascades are functional in normal and osteoarthritic articular chondrocytes. In vivo, we found that IL-1 expression and signaling mechanisms were detectible in the upper zones of normal cartilage, whereas these observations were more pronounced in the upper portions of osteoarthritic cartilage. Given these expression and distribution patterns, our data support two roles for IL-1 in the pathophysiology of articular cartilage. First, chondrocytes in the upper zone of osteoarthritic articular cartilage seem to activate catabolic signaling pathways that may be in response to diffusion of external IL-1 from the synovial fluid. Second, IL-1 seems to be involved in normal cartilage tissue homeostasis as shown by identification of baseline expression patterns and signaling cascade activation.

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