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.
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 mousecartilage 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 mousecartilage, 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 mousecartilage. The expression of β1,2N-acetylglucosaminyltransferase I (GlcNAc-TI) mRNA, which converts high-mannose type N-glycans, was significantly increased in degraded mousecartilage. 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.
Authors: Yea-Rin Lee; Matthew T Briggs; Clifford Young; Mark R Condina; Julia S Kuliwaba; Paul H Anderson; Peter Hoffmann Journal: Anal Bioanal Chem Date: 2022-09-20 Impact factor: 4.478
Authors: Mingcai Zhang; Qinghua Lu; Andrew H Miller; Nicholas C Barnthouse; Jinxi Wang Journal: Int J Biochem Cell Biol Date: 2016-01-20 Impact factor: 5.085
Authors: Yea-Rin Lee; Matthew T Briggs; Mark R Condina; Hamish Puddy; Paul H Anderson; Peter Hoffmann; Julia S Kuliwaba Journal: Int J Mol Sci Date: 2020-09-03 Impact factor: 5.923