{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:55:52Z","timestamp":1790628952553,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Society for Orthopedics and Orthopedic Surgery (DGOOC)","award":["not available"],"award-info":[{"award-number":["not available"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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, \u201cfueling\u201d the HBP by means of glucosamine derivatives or inhibition of deglycosylation turned out as cells and chondroprotectives after cartilage trauma.<\/jats:p>","DOI":"10.3390\/ijms22147247","type":"journal-article","created":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T11:36:44Z","timestamp":1625571404000},"page":"7247","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["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"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0048-5047","authenticated-orcid":false,"given":"Jana","family":"Riegger","sequence":"first","affiliation":[{"name":"Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopedics, University of Ulm, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Baumert","sequence":"additional","affiliation":[{"name":"Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopedics, University of Ulm, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7680-9354","authenticated-orcid":false,"given":"Frank","family":"Zaucke","sequence":"additional","affiliation":[{"name":"Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Department of Orthopaedics (Friedrichsheim), University Hospital Frankfurt, Goethe University, 60528 Frankfurt\/Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf E.","family":"Brenner","sequence":"additional","affiliation":[{"name":"Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopedics, University of Ulm, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/nrrheum.2014.44","article-title":"The individual and socioeconomic impact of osteoarthritis","volume":"10","author":"Hunter","year":"2014","journal-title":"Nat. Rev. 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