2. Academic Validation
  3. Characterization of aberrant glycosylation associated with osteoarthritis based on integrated glycomics methods

Characterization of aberrant glycosylation associated with osteoarthritis based on integrated glycomics methods

  • Arthritis Res Ther. 2023 Jun 12;25(1):102. doi: 10.1186/s13075-023-03084-w.
Hanjie Yu # 1,  Mingxiu Li # 2,  Jian Shu 1,  Liuyi Dang 1,  Xin Wu 1,  Yuzi Wang 1,  Xuan Wang 3,  Xin Chang 2,  Xiaojuan Bao 1,  Bojing Zhu 4,  Xiameng Ren 1,  Wentian Chen 1,  Yi Li 5
Affiliations

Affiliations

  • 1 Laboratory for Functional Glycomics, College of Life Sciences, Northwest University, Xi'an, China.
  • 2 Department of Foot and Ankle Surgery, Honghui Hospital, Xi'an Jiaotong University, 76 Nanguo Road, Xi'an, 710054, Shaanxi Province, China.
  • 3 The Second Clinical Medical College of Shaanxi University of Chinese Medicine, Xianyang, China.
  • 4 College of Life Science, Northwest University, Xi'an, China.
  • 5 Department of Foot and Ankle Surgery, Honghui Hospital, Xi'an Jiaotong University, 76 Nanguo Road, Xi'an, 710054, Shaanxi Province, China. [email protected].
  • # Contributed equally.
PMID: 37308935 DOI: 10.1186/s13075-023-03084-w
Abstract

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.

Keywords

Glycosylation; Intact glycopeptides; LC–MS; Lectin microarray; Osteoarthritis; Site-specific glycosylation.

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