Opposing roles of WNT-5A and WNT-11 in interleukin-1β regulation of type II collagen expression in articular chondrocytes

Abstract

Interleukin (IL)-1β is a major catabolic cytokine that plays a pivotal role in cartilage destruction. This study examined the possible involvement and regulatory mechanisms of Wnt signaling in IL-1β-induced inhibition of type II collagen expression in chondrocytes. Treatment of chondrocytes with IL-1β up-regulated Wnt-5a and down-regulated Wnt-11 expression. Conditioned medium from Wnt-5a-expressing cells inhibited type II collagen expression, whereas knockdown of Wnt-5a by siRNA blocked the inhibitory effects of IL-1β on type II collagen expression. In contrast to the inhibitory effects of Wnt-5a, Wnt-11 stimulated type II collagen expression. Wnt-5a and Wnt-11 did not cause accumulation of β-catenin or activation of the β-catenin-Tcf/Lef transcriptional complex. Instead, we found that Wnt-5a activated c-Jun N-terminal kinase and that an inhibitor of this kinase blocked Wnt-5a inhibition of type II collagen expression. In contrast, Wnt-11 activated protein kinase C and an inhibitor of this kinase blocked Wnt-11 stimulation of type II collagen expression. Collectively, these results indicate that Wnt-5a and Wnt-11 signaling through distinct non-canonical Wnt pathways have opposing effects on type II collagen expression by chondrocytes. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.