Alterations of high-mannose type N-glycosylation in human and mouse osteoarthritis cartilage
Autor: | Norimasa Iwasaki, Shin-Ichiro Nishimura, Naoki Seito, Tomoya Matsuhashi, Maho Amano, Megumi Hato, Tomohiro Onodera, Atsushi Urita, Hiroaki Nakagawa, Akio Minami |
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Rok vydání: | 2011 |
Předmět: |
Adult
Cartilage Articular Pathology medicine.medical_specialty Glycosylation Immunology Stimulation Osteoarthritis Matrix metalloproteinase N-Acetylglucosaminyltransferases Pathogenesis Mice Chondrocytes Rheumatology N-linked glycosylation Polysaccharides Matrix Metalloproteinase 13 medicine Animals Humans Immunology and Allergy Pharmacology (medical) Aged Aged 80 and over Gene knockdown Messenger RNA Chemistry Cartilage Middle Aged medicine.disease Cell biology carbohydrates (lipids) ADAM Proteins medicine.anatomical_structure Female ADAMTS5 Protein |
Zdroj: | Arthritis & Rheumatism. 63:3428-3438 |
ISSN: | 0004-3591 |
Popis: | Objective The process of N-glycosylation is involved in the pathogenesis of various diseases. However, little is known about the contribution of changes in N-glycans in osteoarthritis (OA). The aim of this study was to identify the alterations in N-glycans in human OA cartilage, to characterize the messenger RNA (mRNA) expression of N-glycan biosynthesis enzyme genes (N-glycogenes) in mouse articular chondrocytes during cartilage degradation, and to analyze the relationship between altered N-glycan patterns and mechanisms of cartilage degradation. Methods Alterations in N-glycans were analyzed in human OA cartilage and degraded mouse cartilage by high-performance liquid chromatography and mass spectrometry. N-glycogene mRNA expression in mouse chondrocytes was measured using reverse transcription–polymerase chain reaction. To assess the relationship between the altered N-glycans and degradation of mouse cartilage, experiments involving either knockdown or overexpression of N-glycogenes were performed in mouse articular chondrocytes. Results Alterations in high-mannose type N-glycans were observed in both human OA cartilage and degraded mouse cartilage. The expression of β1,2N-acetylglucosaminyltransferase I (GlcNAc-TI) mRNA, which converts high-mannose type N-glycans, was significantly increased in degraded mouse cartilage. Mouse chondrocytes with suppressed GlcNAc-TI expression had reduced levels of matrix metalloproteinase 13 (MMP-13) and ADAMTS-5 (aggrecanase 2) mRNA following stimulation with interleukin-1α (IL-1α). In contrast, mouse chondrocytes overexpressing GlcNAc-TI had increased levels of MMP-13 and ADAMTS-5 mRNA following stimulation with IL-1α. Conclusion These findings indicate that alterations in high-mannose type N-glycans and N-glycogenes in chondrocytes correlate with the release of MMP-13 and ADAMTS-5 during cartilage degradation. These findings suggest that N-glycans play a crucial role in the initiation and progression of OA. |
Databáze: | OpenAIRE |
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