title: Alterations of high-mannose type N-glycosylation in human and mouse osteoarthritis cartilage.
abstract: 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.
  
  
  CONCLUSIONS
  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.affiliation: Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Urita
authors.forename: Tomoya
authors.initials: T
authors.lastname: Matsuhashi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Onodera
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Megumi
authors.initials: M
authors.lastname: Hato
authors.forename: Maho
authors.initials: M
authors.lastname: Amano
authors.forename: Naoki
authors.initials: N
authors.lastname: Seito
authors.forename: Akio
authors.initials: A
authors.lastname: Minami
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Nishimura
authors.forename: Norimasa
authors.initials: N
authors.lastname: Iwasaki
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000071116:ADAMTS5 Protein; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006031:Glycosylation; D006801:Humans; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D011134:Polysaccharides / Q000378:metabolism*
chemical_list: D011134:Polysaccharides; D017351:N-Acetylglucosaminyltransferases; C024850:alpha-1,3-mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferase I; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human; D053509:Matrix Metalloproteinase 13