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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 
 

Role of Wnt-5A in interleukin-1beta-induced matrix metalloproteinase expression in rabbit temporomandibular joint condylar chondrocytes.

OBJECTIVE: To determine the possible involvement and regulatory mechanisms of Wnt-5A signaling in interleukin-1beta (IL-1beta)-induced increase in matrix metalloproteinase 1 (MMP-1), MMP-3, MMP-9, and MMP-13 expression in temporomandibular joint (TMJ) condylar chondrocytes. METHODS: Primary rabbit condylar chondrocytes were treated with IL-1beta, purified Wnt-5A protein, or both and transfected with Wnt-5A expression vector. Expression of Wnt-5A, MMP-1, MMP-3, MMP-9, MMP-13, and type II collagen, as well as cell morphologic changes, were examined. To explore the mechanisms of action of Wnt-5A, the accumulation and nuclear translocation of beta-catenin, the transcription activity of the beta-catenin-Tcf/Lef complex, phosphorylated JNK, phosphorylated ERK, and phosphorylated p38 were analyzed. SP600125, a JNK inhibitor, was used to investigate the role of the JNK pathway in Wnt-5A induction of MMP-1, MMP-3, MMP-9, and MMP-13. RESULTS: Treatment of rabbit condylar chondrocytes with IL-1beta up-regulated Wnt-5A expression. Purified Wnt-5A protein and transfection with Wnt-5A expression vector promoted the expression of MMP-1, MMP-3, MMP-9, and MMP-13. Wnt-5A did not cause accumulation and nuclear translocation of beta-catenin or activation of the beta-catenin-Tcf/Lef transcription complex. Instead, Wnt-5A activated JNK, and an inhibitor of JNK blocked the Wnt-5A-induced up-regulated expression of MMPs. CONCLUSION: These findings indicate that IL-1beta up-regulates Wnt-5A, and the activation of Wnt-5A signaling induces the expression of MMP-1, MMP-3, MMP-9, and MMP-13 via the JNK signaling pathway in rabbit TMJ condylar chondrocytes. Blockage of JNK signaling impairs the Wnt-5A-induced up-regulation of MMPs. Thus, Wnt-5A may be associated with cartilage destruction by promoting the expression of MMPs.[1]

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