Decrease of core 2 O-glycans on synovial lubricin in osteoarthritis reduces galectin-3 mediated crosslinking
Artikel i vetenskaplig tidskrift, 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
Författare
Sarah A. Flowers
Göteborgs universitet
Kristina A. Thomsson
Göteborgs universitet
Liaqat Ali
Göteborgs universitet
Shan Huang
Göteborgs universitet
Yolanda Mthembu
Göteborgs universitet
Suresh C. Regmi
University of Calgary
Jan Holgersson
Göteborgs universitet
Tannin A. Schmidt
UConn Health
Ola Rolfson
Göteborgs universitet
Lena I. Björkman
Göteborgs universitet
Martina Sundqvist
Göteborgs universitet
Anna Karlsson-Bengtsson
Göteborgs universitet
Chalmers, Biologi och bioteknik, Kemisk biologi
Gregory D. Jay
The Warren Alpert Medical School
Thomas Eisler
Danderyds sjukhus
Roman Krawetz
Cumming School of Medicine
McCaig Institute for Bone and Joint Health
Niclas G. Karlsson
Göteborgs universitet
Journal of Biological Chemistry
0021-9258 (ISSN) 1083-351X (eISSN)
Vol. 295 47 16023-16036Ämneskategorier
Biokemi och molekylärbiologi
Annan medicinsk grundvetenskap
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
DOI
10.1074/jbc.RA120.012882
PubMed
32928962