15-Deoxy-delta 12,14-ProstaglandinJ2 Regulates Dedifferentiation through Peroxisome Proliferator-Activated Receptor-gamma-Dependent Pathway but Not COX-2 Expression in Articular Chondrocytes.
10.3346/jkms.2007.22.5.891
- Author:
Ji Hye LEE
1
;
Seon Mi YU
;
Eun Kyung YOON
;
Won Kil LEE
;
Jae Chang JUNG
;
Song Ja KIM
Author Information
1. Department of Biological Sciences, College of Natural Sciences, Kongju National University, Gongju, Korea. ksj85@kongju.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Cell Differentiation;
Cyclooxygenase 2;
PPAR Gamma;
Chondrocytes
- MeSH:
Animals;
Arteries/*metabolism;
Cell Differentiation;
Chondrocytes/*metabolism;
Cyclooxygenase 2/*metabolism;
Dinoprostone/metabolism;
Dose-Response Relationship, Drug;
*Gene Expression Regulation, Enzymologic;
Genes, Reporter;
Immunoblotting;
PPAR gamma/*metabolism;
Prostaglandin D2/*analogs & derivatives/metabolism;
Rabbits;
Time Factors;
Transfection
- From:Journal of Korean Medical Science
2007;22(5):891-897
- CountryRepublic of Korea
- Language:English
-
Abstract:
Peroxisome proliferator-activated receptors-gamma (PPAR-gamma) is critical for phenotype determination at early differentiation stages of mesenchymal cells, whereas its physiological role is unclear. Therefore, we investigated the role of 15-deoxy-delta 12,14-prostaglandinJ2 (15d-PGJ2), the natural receptor ligand for PPAR-gamma, on dedifferentiation and inflammatory responses, such as COX-2 expression and PGE2 production, in articular chondrocytes. Our data indicate that the 15d-PGJ2 caused a loss of differentiated chondrocyte phenotype as demonstrated by inhibition of type II collagen and proteoglycan synthesis. 15d-PGJ2 also induced COX-2 expression and PGE2 production. The 15d-PGJ2-induced dedifferentiation effect seems to be dependent on PPAR-gamma activation, as the PPRE luciferase activity increased and PPAR-gamma antagonist, BADGE, abolished type II collagen expression. However, BADGE did not block 15d-PGJ2-induced COX-2 expression. Collectively, our findings suggest that PPAR-gamma-dependent and -independent mechanisms of 15d-PGJ2-induced dedifferentiation and inflammatory responses in articular chondrocytes, respectively. Additionally, these data suggest that targeted modulation of the PPAR-gamma pathway may offer a novel approach for therapeutic inhibition of joint tissue degradation.
