@article{4e47b6cfd6e84e009fe44fe0ea255401,
title = "Decrease of core 2 O-glycans on synovial lubricin in osteoarthritis reduces galectin-3 mediated crosslinking",
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{\textquoteright}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.",
author = "Flowers, {Sarah A.} and Thomsson, {Kristina A.} and Liaqat Ali and Shan Huang and Yolanda Mthembu and Regmi, {Suresh C.} and Jan Holgersson and Schmidt, {Tannin A.} and Ola Rolfson and Bj{\"o}rkman, {Lena I.} and Martina Sundqvist and Anna Karlsson-Bengtsson and Jay, {Gregory D.} and Thomas Eisler and Roman Krawetz and Karlsson, {Niclas G.}",
note = "Funding Information: Funding and additional information—This study was funded by grants from the Swedish state under the agreement between the Swedish government and the county council, the ALF-agreement Grants ALFGBG-722391 (to N. G. K.) and ALFGBG-726801 (J. H.), the Swedish Research Council Grants 621-2013-5895 (to N. G. K.) and 2018-03077 (A.K.), Kung Gustav V:s 80-year foundation (N. G. K. ), Petrus and Augusta Hedlund{\textquoteright}s foundation Grant M-2016-0353 (to N. G. K.), AFA insurance research fund Grant dnr 150150 (to N. G. K.), and National Institute of Health R01AR067748 (to G. D. J.). Funding Information: This study was funded by grants from the Swedish state under the agreement between the Swedish government and the county council, the ALF-agreement Grants ALFGBG-722391 (to N. G. K.) and ALFGBG-726801 (J. H.), the Swedish Research Council Grants 621-2013-5895 (to N. G. K.) and 2018-03077 (A.K.), Kung Gustav V:s 80-year foundation (N. G. K.), Petrus and Augusta Hedlund?s foundation Grant M-2016-0353 (to N. G. K.), AFA insurance research fund Grant dnr 150150 (to N. G. K.), and National Institute of Health R01AR067748 (to G. D. J.). Publisher Copyright: {\textcopyright} 2020 Flowers et al.",
year = "2020",
month = nov,
day = "20",
doi = "10.1074/jbc.RA120.012882",
language = "English (US)",
volume = "295",
pages = "16023--16036",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "47",
}