Opposing roles of WNT-5A and WNT-11 in interleukin-1beta regulation of type II collagen expression in articular chondrocytes.
Interleukin (IL)-1beta 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-1beta-induced inhibition of type II collagen expression in chondrocytes. Treatment of chondrocytes with IL-1beta 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-1beta 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 beta-catenin or activation of the beta-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.
Ryu
Je-Hwang
JH
Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea.
Chun
Jang-Soo
JS
Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea. Electronic address: jschun@gist.ac.kr.
D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology*; D019902:Chondrocytes / Q000378:metabolism*; D024043:Collagen Type II / Q000235:genetics*; D005786:Gene Expression Regulation; D007375:Interleukin-1 / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction; D051153:Wnt Proteins / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
D024043:Collagen Type II; D007375:Interleukin-1; D051153:Wnt Proteins; D051176:beta Catenin; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases