- search hit 1 of 1
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
- 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.
Author: | Jana RieggerORCiDGND, Julia Baumert, Frank ZauckeORCiDGND, Rolf E. Brenner |
---|---|
URN: | urn:nbn:de:hebis:30:3-622025 |
DOI: | https://doi.org/10.3390/ijms22147247 |
ISSN: | 1422-0067 |
ISSN: | 1661-6596 |
Parent Title (English): | International journal of molecular sciences |
Publisher: | Molecular Diversity Preservation International |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2021/07/06 |
Date of first Publication: | 2021/07/06 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2023/01/20 |
Tag: | O-GlcNAcylation; cartilage trauma; cell death; chondrocytes; glucosamine; hexosamine biosynthetic pathway; post-traumatic osteoarthritis; therapy |
Volume: | 22 |
Issue: | 14 |
Article Number: | 7247 |
Page Number: | 16 |
First Page: | 1 |
Last Page: | 16 |
Note: | Correspondence: Rolf E. Brenner; Tel.: +49-731-500-63280 |
Note: | 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. |
HeBIS-PPN: | 505601710 |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit | |
Sammlungen: | Universitätspublikationen |
Licence (German): | ![]() |