Decrease of core 2 O-glycans on synovial lubricin in osteoarthritis reduces galectin-3 mediated crosslinking
Journal article, 2020

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.





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Sarah A. Flowers

University of Gothenburg

Kristina A. Thomsson

University of Gothenburg

Liaqat Ali

University of Gothenburg

Shan Huang

University of Gothenburg

Yolanda Mthembu

University of Gothenburg

Suresh C. Regmi

University of Calgary

Jan Holgersson

University of Gothenburg

Tannin A. Schmidt

UConn Health

Ola Rolfson

University of Gothenburg

Lena I. Björkman

University of Gothenburg

Martina Sundqvist

University of Gothenburg

Anna Karlsson-Bengtsson

University of Gothenburg

Chalmers, Biology and Biological Engineering, Chemical Biology

Gregory D. Jay

The Warren Alpert Medical School

Thomas Eisler

Danderyd Hospital

Roman Krawetz

Cumming School of Medicine

McCaig Institute for Bone and Joint Health

Niclas G. Karlsson

University of Gothenburg

Journal of Biological Chemistry

0021-9258 (ISSN) 1083-351X (eISSN)

Vol. 295 47 16023-16036

Subject Categories

Biochemistry and Molecular Biology

Other Basic Medicine

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)





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