Beta-catenin regulates expression of cyclooxygenase-2 in articular chondrocytes.
Pro-inflammatory cytokine such as interleukin (IL)-1beta causes inflammation of articular cartilage via induction of cyclooxygenase (COX)-2 expression. We investigated in this study the role of beta-catenin in the IL-1beta regulation of COX-2 expression in articular chondrocytes. IL-1beta increased expression of COX-2 and induced accumulation and nuclear translocation of transcriptionally competent beta-catenin. Inhibition of beta-catenin degradation by the treatment of cells with LiCl or proteasome inhibitor stimulated expression of COX-2, indicating that transcriptionally active beta-catenin is sufficient to induce COX-2 expression. This was demonstrated further by the observation that ectopic expression of transcriptionally competent beta-catenin stimulated expression of COX-2. Levels of beta-catenin and COX-2 protein were increased in osteoarthritic and rheumatoid arthritic cartilage, suggesting that beta-catenin may play a role in the inflammatory responses of arthritic cartilage. Taken together, our data suggest that accumulation of transcriptionally active beta-catenin contributes to the expression of COX-2 in articular chondrocytes.
Kim
Song Ja
SJ
Department of Life Science, Kwangju Institute of Science and Technology, 500-712, Gwangju, Republic of Korea.
Im
Dae Seong
DS
Kim
Seon Hee
SH
Ryu
Je Hwang
JH
Hwang
Sang Gu
SG
Seong
Je Kyung
JK
Chun
Churl Hong
CH
Chun
Jang Soo
JS
D000818:Animals; D001168:Arthritis / Q000201:enzymology / Q000378:metabolism; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D003598:Cytoskeletal Proteins / Q000378:metabolism / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D011817:Rabbits; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation / Q000187:drug effects; D051176:beta Catenin
D003598:Cytoskeletal Proteins; D007375:Interleukin-1; D007527:Isoenzymes; D015534:Trans-Activators; D051176:beta Catenin; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases