O-linked N-acetylglucosamine (O-GlcNAc) protein modification is increased in the cartilage of patients with knee osteoarthritis

• Published in: Osteoarthritis and cartilage 2014-02, Vol.22 (2), p.259-263
• Main Authors: Tardio, L, Andrés-Bergós, J, Zachara, N.E, Larrañaga-Vera, A, Rodriguez-Villar, C, Herrero-Beaumont, G, Largo, R
• Format: Article
• Language: English
• Subjects: Acetylglucosamine - metabolism; Acylation; Adult; beta-N-Acetylhexosaminidases - biosynthesis; Cartilage; Cartilage, Articular - metabolism; Cartilage, Articular - pathology; Case-Control Studies; Cell Differentiation - physiology; Cells, Cultured; Chondrocytes; Chondrocytes - drug effects; Chondrocytes - metabolism; Female; Glycosylation; Humans; Hypertrophic differentiation; Inflammation Mediators - pharmacology; Interleukin-1 - pharmacology; Isoenzymes - biosynthesis; Male; Middle Aged; N-Acetylglucosaminyltransferases - biosynthesis; O-GlcNAcylation; Osteoarthritis, Knee - metabolism; Osteoarthritis, Knee - pathology; Protein Modification, Translational - drug effects; Protein Modification, Translational - physiology; Rheumatology
• ISSN: 1063-4584; 1522-9653
• DOI: 10.1016/j.joca.2013.12.001

Summary Objective There is increasing evidence that the addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins plays an important role in cell signaling pathways. In chondrocytes, accumulation of O-GlcNAc-modified proteins induces hypertrophic differentiation. Osteoarthritis (OA) is characterized by cartilage degradation, and hypertrophic-like changes in hyaline chondrocytes. However, the mechanisms responsible for these changes have not been described. Our aim was to study whether O-GlcNAcylation and the enzymes responsible for this modification are dysregulated in the cartilage of patients with knee OA and whether interleukin-1 could induce these modifications in cultured human OA chondrocytes (HOC). Design Human cartilage was obtained from patients with knee OA and from age and sex-matched healthy donors. HOC were cultured and stimulated with the catabolic cytokine IL-1α. Global protein O-GlcNAcylation and the synthesis of the key enzymes responsible for this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), were assessed by western blot. Results OA was associated with a 4-fold increase in the global O-GlcNAcylation in the cartilage. OA cartilage showed a re-distribution of the OGT and OGA isoforms, with a net increase in the presence of both enzymes, in comparison to healthy cartilage. In HOC, IL-1α stimulation rapidly increased O-GlcNAcylation and OGT and OGA synthesis. Conclusions Our results indicate that a proinflammatory milieu could favor the accumulation of O-GlcNAcylated proteins in OA cartilage, together with the dysregulation of the enzymes responsible for this modification. The increase in O-GlcNAcylation could be responsible, at least partially, for the re-expression of hypertrophic differentiation markers that have been observed in OA.