ERK-1/-2 and p38 Kinase Oppositely Regulate 15-deoxy-delta(12,14)-prostaglandinJ2-Induced PPAR-gamma Activation That Mediates Dedifferentiation But Not Cyclooxygenase-2 Expression in Articular Chondrocytes.
10.3346/jkms.2007.22.6.1015
- Author:
Eun Kyung YOON
1
;
Won Kil LEE
;
Ji Hye LEE
;
Seon Mi YU
;
Sang Gu HWANG
;
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:
Cyclooxygenase 2;
Dedifferentiation;
Map Kinase
- MeSH:
Animals;
Cartilage, Articular/*cytology;
Cell Differentiation/drug effects;
Chondrocytes/cytology/*drug effects/metabolism;
Cyclooxygenase 2/*analysis;
Dinoprostone/biosynthesis;
Mitogen-Activated Protein Kinase 1/*physiology;
Mitogen-Activated Protein Kinase 3/*physiology;
PPAR gamma/*physiology;
Prostaglandin D2/*analogs & derivatives/pharmacology;
Rabbits;
p38 Mitogen-Activated Protein Kinases/*physiology
- From:Journal of Korean Medical Science
2007;22(6):1015-1021
- CountryRepublic of Korea
- Language:English
-
Abstract:
Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a ligand-activated transcription factor and plays an important role in growth, differentiation, and inflammation in different tissues. In this study, we investigated the effects of 15d-PGJ2, a high-affinity ligand of PPAR-gamma, on dedifferentiation and on inflammatory responses such as COX-2 expression and PGE2 production in rabbit articular chondrocytes with a focus on ERK-1/-2, p38 kinase, and PPAR-gamma activation. We report here that 15d-PGJ2 induced dedifferentiation and/or COX-2 expression and subsequent PGE2 production. 15d-PGJ2 treatment stimulated activation of ERK-1/-2, p38 kinase, and PPAR-gamma. Inhibition of ERK-1/-2 with PD98059 recovered 15d-PGJ2-induced dedifferentiation and enhanced PPAR-gamma activation, whereas inhibition of p38 kinase with SB203580 potentiated dedifferentiation and partially blocked PPAR-gamma activation. Inhibition of ERK-1/-2 and p38 kinase abolished 15d-PGJ2-induced COX-2 expression and subsequent PGE2 production. Our findings collectively suggest that ERK-1/-2 and p38 kinase oppositely regulate 15d-PGJ2-induced dedifferentiation through a PPAR-gamma-dependent mechanism, whereas COX-2 expression and PGE2 production is regulated by ERK-1/-2 through a PPAR-gamma-independent mechanism but not p38 kinase in articular chondrocytes. Additionally, these data suggest that targeted modulation of the PPAR-gamma and mitogen-activated protein kinase pathway may offer a novel approach for therapeutic inhibition of joint tissue degradation.
