Characterization of aberrant glycosylation associated with osteoarthritis based on integrated glycomics methods.
Glycosylation
Intact glycopeptides
LC–MS
Lectin microarray
Osteoarthritis
Site-specific glycosylation
Journal
Arthritis research & therapy
ISSN: 1478-6362
Titre abrégé: Arthritis Res Ther
Pays: England
ID NLM: 101154438
Informations de publication
Date de publication:
12 06 2023
12 06 2023
Historique:
received:
12
04
2023
accepted:
03
06
2023
medline:
14
6
2023
pubmed:
13
6
2023
entrez:
12
6
2023
Statut:
epublish
Résumé
Osteoarthritis (OA) is the most common form of arthritis, affecting millions of aging people. Investigation of abnormal glycosylation is essential for the understanding of pathological mechanisms of OA. The total protein was isolated from OA (n = 13) and control (n = 11) cartilages. Subsequently, glycosylation alterations of glycoproteins in OA cartilage were investigated by lectin microarrays and intact glycopeptides analysis. Finally, the expression of glycosyltransferases involved in the synthesis of altered glycosylation was assessed by qPCR and GEO database. Our findings revealed that several glycopatterns, such as α-1,3/6 fucosylation and high-mannose type of N-glycans were altered in OA cartilages. Notably, over 27% of identified glycopeptides (109 glycopeptides derived from 47 glycoproteins mainly located in the extracellular region) disappeared or decreased in OA cartilages, which is related to the cartilage matrix degradation. Interestingly, the microheterogeneity of N-glycans on fibronectin and aggrecan core protein was observed in OA cartilage. Our results combined with GEO data indicated that the pro-inflammatory cytokines altered the expression of glycosyltransferases (ALG3, ALG5, MGAT4C, and MGAT5) which may contribute to the alterations in glycosylation. Our study revealed the abnormal glycopatterns and heterogeneities of site-specific glycosylation associated with OA. To our knowledge, it is the first time that the heterogeneity of site-specific N-glycans was reported in OA cartilage. The results of gene expression analysis suggested that the expression of glycosyltransferases was impacted by pro-inflammatory cytokines, which may facilitate the degradation of protein and accelerate the process of OA. Our findings provide valuable information for the understanding of molecular mechanisms in the pathogenesis of OA.
Sections du résumé
BACKGROUND
Osteoarthritis (OA) is the most common form of arthritis, affecting millions of aging people. Investigation of abnormal glycosylation is essential for the understanding of pathological mechanisms of OA.
METHODS
The total protein was isolated from OA (n = 13) and control (n = 11) cartilages. Subsequently, glycosylation alterations of glycoproteins in OA cartilage were investigated by lectin microarrays and intact glycopeptides analysis. Finally, the expression of glycosyltransferases involved in the synthesis of altered glycosylation was assessed by qPCR and GEO database.
RESULTS
Our findings revealed that several glycopatterns, such as α-1,3/6 fucosylation and high-mannose type of N-glycans were altered in OA cartilages. Notably, over 27% of identified glycopeptides (109 glycopeptides derived from 47 glycoproteins mainly located in the extracellular region) disappeared or decreased in OA cartilages, which is related to the cartilage matrix degradation. Interestingly, the microheterogeneity of N-glycans on fibronectin and aggrecan core protein was observed in OA cartilage. Our results combined with GEO data indicated that the pro-inflammatory cytokines altered the expression of glycosyltransferases (ALG3, ALG5, MGAT4C, and MGAT5) which may contribute to the alterations in glycosylation.
CONCLUSION
Our study revealed the abnormal glycopatterns and heterogeneities of site-specific glycosylation associated with OA. To our knowledge, it is the first time that the heterogeneity of site-specific N-glycans was reported in OA cartilage. The results of gene expression analysis suggested that the expression of glycosyltransferases was impacted by pro-inflammatory cytokines, which may facilitate the degradation of protein and accelerate the process of OA. Our findings provide valuable information for the understanding of molecular mechanisms in the pathogenesis of OA.
Identifiants
pubmed: 37308935
doi: 10.1186/s13075-023-03084-w
pii: 10.1186/s13075-023-03084-w
pmc: PMC10258941
doi:
Substances chimiques
Glycoproteins
0
Cytokines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
102Informations de copyright
© 2023. The Author(s).
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