15-deoxy-Delta 12,14-ProstaglandinJ2 regulates dedifferentiation through peroxisome proliferator-activated receptor-gamma-dependent pathway but not COX-2 expression in articular chondrocytes.
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.
Lee
Ji-Hye
JH
Department of Biological Sciences, College of Natural Sciences, Kongju National University, Gongju, Korea.
Yu
Seon-Mi
SM
Yoon
Eun-Kyung
EK
Lee
Won-Kil
WK
Jung
Jae-Chang
JC
Kim
Song-Ja
SJ
D000818:Animals; D001158:Arteries / Q000378:metabolism*; D002454:Cell Differentiation; D019902:Chondrocytes / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D015151:Immunoblotting; D047495:PPAR gamma / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000378:metabolism; D011817:Rabbits; D013997:Time Factors; D014162:Transfection
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D047495:PPAR gamma; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D015230:Prostaglandin D2