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.

lubricin

glycobiology

glycomics

mucin

osteoarthritis

sialic acid

galectin

biolubrication

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

Rektor

Göteborgs universitet

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 16023-16036

Ämneskategorier

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

Mer information

Senast uppdaterat

2020-12-10