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.
glycomics
osteoarthritis
lubricin
glycobiology
sialic acid
galectin
biolubrication
mucin
Author
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 16023-16036Subject 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)
DOI
10.1074/jbc.RA120.012882
PubMed
32928962