|dc.contributor.author||S G Hwang||-|
|dc.contributor.author||S S Yu||-|
|dc.contributor.author||J S Chun||-|
|dc.description.abstract||Interleukin (IL)-1β is a major catabolic pro-inflammatory cytokine involved in cartilage destruction-associated processes, such as loss of the differentiated chondrocyte phenotype (dedifferentiation) and inflammation. Here, we investigated the role of c-Jun and activator protein-1 (AP-1) in IL-1β-induced dedifferentiation and cyclooxygenase (COX)-2 expression in primary cultured chondrocytes. IL-1β induced expression and transient phosphorylation of c-Jun in primary cultured chondrocytes. Ectopic expression of c-Jun was sufficient to cause dedifferentiation, whereas expression of dominant negative c-Jun blocked IL-1β-induced dedifferentiation. Interestingly, modulation of c-Jun expression did not affect IL-1β-induced COX-2 expression. Further experiments revealed that c-Jun phosphorylation was mediated by c-Jun N-terminal kinase and was required for IL-1β-induced dedifferentiation but not COX-2 expression. Consistent with its ability to induce phosphorylation of c-Jun, IL-1β caused transient activation of AP-1, which is necessary for IL-1β-induced dedifferentiation. IL-1β treatment suppressed expression of Sox-9, a major transcription factor that regulates type II collagen expression. Inhibition of c-Jun N-terminal kinase or AP-1 reversed IL-1β-induced suppression of Sox-9, and ectopic expression of c-Jun was sufficient to cause suppression of Sox-9. Our results collectively suggest that IL-1β suppresses type II collagen expression in articular chondrocytes by inducing expression and phosphorylation of c-Jun, AP-1 activation, and subsequent suppression of Sox-9.||-|
|dc.publisher||Amer Soc Biochemistry Molecular Biology Inc||-|
|dc.title||c-Jun/activator protein-1 mediates interleukin-1β-induced dedifferentiation but not cyclooxygenase-2 expression in articular chondrocytes||-|
|dc.title.alternative||c-Jun/activator protein-1 mediates interleukin-1beta-induced dedifferentiation but not cyclooxygenase-2 expression in articular chondrocytes||-|
|dc.citation.title||Journal of Biological Chemistry||-|
|dc.identifier.bibliographicCitation||Journal of Biological Chemistry, vol. 280, no. 33, pp. 29780-29787||-|
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