Fiche publication
Date publication
octobre 2014
Journal
Biochemical and biophysical research communications
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MAGDALOU Jacques
Tous les auteurs :
Wen Y, Qin J, Deng Y, Wang H, Magdalou J, Chen L
Lien Pubmed
Résumé
UDP-galactose-4-epimerase (GALE) is a key enzyme catalyzing the interconversion of UDP-glucose and UDP-galactose, as well as UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine, which are all precursors for the proteoglycans (PGs) synthesis. However, whether GALE is essential in cartilage homeostasis remains unknown. Therefore, we investigated the role of GALE in PGs synthesis of human articular chondrocytes, the GALE expression in OA, and the regulation of GALE expression by interleukin-1beta (IL-1β). Silencing GALE gene with specific siRNAs resulted in a markedly inhibition of PGs synthesis in human articular chondrocytes. GALE protein levels were also decreased in both human and rat OA cartilage, thus leading to losses of PGs contents. Moreover, GALE mRNA expression was stimulated by IL-1β in early phase, but suppressed in late phase, while the suppression of GALE expression induced by IL-1β was mainly mediated by stress-activated protein kinase/c-Jun N-terminal kinase pathway. These data indicated a critical role of GALE in maintaining cartilage homeostasis, and suggested that GALE inhibition might contribute to OA progress.
Mots clés
Aged, Cartilage, Articular, metabolism, Cells, Cultured, Chondrocytes, metabolism, Female, Humans, Knee Joint, metabolism, Male, Osteoarthritis, Knee, metabolism, Proteoglycans, biosynthesis, UDPglucose 4-Epimerase, metabolism
Référence
Biochem. Biophys. Res. Commun.. 2014 Oct 3;452(4):906-11
