Back to Search
Start Over
The critical role of UDP-galactose-4-epimerase in osteoarthritis: modulating proteoglycans synthesis of the articular chondrocytes.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2014 Oct 03; Vol. 452 (4), pp. 906-11. Date of Electronic Publication: 2014 Sep 06. - Publication Year :
- 2014
-
Abstract
- 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.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Subjects :
- Aged
Cartilage, Articular pathology
Cells, Cultured
Chondrocytes pathology
Female
Humans
Male
Osteoarthritis, Knee pathology
Cartilage, Articular metabolism
Chondrocytes metabolism
Knee Joint metabolism
Knee Joint pathology
Osteoarthritis, Knee metabolism
Proteoglycans biosynthesis
UDPglucose 4-Epimerase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 452
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 25201731
- Full Text :
- https://doi.org/10.1016/j.bbrc.2014.08.148