TY  - JOUR
A1  - Riegger, Jana
A1  - Baumert, Julia
A1  - Zaucke, Frank
A1  - Brenner, Rolf E.
T1  - The hexosamine biosynthetic pathway as a therapeutic target after cartilage trauma: modification of chondrocyte survival and metabolism by glucosamine derivatives and PUGNAc in an ex vivo model
T2  - International journal of molecular sciences
N2  - The hexosamine biosynthetic pathway (HBP) is essential for the production of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), the building block of glycosaminoglycans, thus playing a crucial role in cartilage anabolism. Although O-GlcNAcylation represents a protective regulatory mechanism in cellular processes, it has been associated with degenerative diseases, including osteoarthritis (OA). The present study focuses on HBP-related processes as potential therapeutic targets after cartilage trauma. Human cartilage explants were traumatized and treated with GlcNAc or glucosamine sulfate (GS); PUGNAc, an inhibitor of O-GlcNAcase; or azaserine (AZA), an inhibitor of GFAT-1. After 7 days, cell viability and gene expression analysis of anabolic and catabolic markers, as well as HBP-related enzymes, were performed. Moreover, expression of catabolic enzymes and type II collagen (COL2) biosynthesis were determined. Proteoglycan content was assessed after 14 days. Cartilage trauma led to a dysbalanced expression of different HBP-related enzymes, comparable to the situation in highly degenerated tissue. While GlcNAc and PUGNAc resulted in significant cell protection after trauma, only PUGNAc increased COL2 biosynthesis. Moreover, PUGNAc and both glucosamine derivatives had anti-catabolic effects. In contrast, AZA increased catabolic processes. Overall, “fueling” the HBP by means of glucosamine derivatives or inhibition of deglycosylation turned out as cells and chondroprotectives after cartilage trauma.
KW  - hexosamine biosynthetic pathway
KW  - cartilage trauma
KW  - post-traumatic osteoarthritis
KW  - chondrocytes
KW  - O-GlcNAcylation
KW  - glucosamine
KW  - cell death
KW  - therapy
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62202
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-622025
SN  - 1422-0067
SN  - 1661-6596
N1  - Correspondence: Rolf E. Brenner; Tel.: +49-731-500-63280
N1  - This research study was funded by the Deutsche Initiative Arthroseforschung of the German Society of Orthopedics and Orthopedic Surgery (DGOOC).Moreover, this project was supported by the European Social Fund and by theMinistry of Science, Research and Arts Baden-Württemberg.
VL  - 22
IS  - 14
SP  - 1
EP  - 16
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -