Decrease of core 2 O-glycans on synovial lubricin in osteoarthritis reduces galectin-3 mediated crosslinking

Sarah A. Flowers, Kristina A. Thomsson, Liaqat Ali, Shan Huang, Yolanda Mthembu, Suresh C. Regmi, Jan Holgersson, Tannin A. Schmidt, Ola Rolfson, Lena I. Björkman, Martina Sundqvist, Anna Karlsson-Bengtsson, Gregory D. Jay, Thomas Eisler, Roman Krawetz, Niclas G. Karlsson

Research output: Contribution to journalArticlepeer-review

Abstract

The synovial fluid glycoprotein lubricin (also known as proteoglycan 4) is a mucin-type O-linked glycosylated biological lubricant implicated to be involved in osteoarthritis (OA) development. Lubricin’s ability to reduce friction is related to its glycosylation consisting of sialylated and unsialylated Tn-antigens and core 1 and core 2 structures. The glycans on lubricin have also been suggested to be involved in crosslinking and stabilization of the lubricating superficial layer of cartilage by mediating interaction between lubricin and galectin-3. However, with the spectrum of glycans being found on lubricin, the glycan candidates involved in this interaction were unknown. Here, we confirm that the core 2 O-linked glycans mediate this lubricin–galectin-3 interaction, shown by surface plasmon resonance data indicating that recombinant lubricin (rhPRG4) devoid of core 2 structures did not bind to recombinant galectin-3. Conversely, transfection of Chinese hamster ovary cells with the core 2 GlcNAc transferase acting on a mucin-type O-glycoprotein displayed increased galectin-3 binding. Both the level of galectin-3 and the galectin-3 interactions with synovial lubricin were found to be decreased in late-stage OA patients, coinciding with an increase in unsialylated core 1 O-glycans (T-antigens) and Tn-antigens. These data suggest a defect in crosslinking of surface-active molecules in OA and provide novel insights into OA molecular pathology.

Original languageEnglish (US)
Pages (from-to)16023-16036
Number of pages14
JournalJournal of Biological Chemistry
Volume295
Issue number47
DOIs
StatePublished - Nov 20 2020

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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