Decrease of core-2 O-glycans on synovial lubricin in osteoarthritis reduces galectin-3 mediated crosslinking.,Journal of Biological Chemistry

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Decrease of core-2 O-glycans on synovial lubricin in osteoarthritis reduces galectin-3 mediated crosslinking.
Journal of Biological Chemistry ( IF 4.0 ) Pub Date : 2020-11-20 , DOI: 10.1074/jbc.ra120.012882
Sarah A Flowers ₁ , Kristina A Thomsson ₁ , Liaqat Ali ₁ , Shan Huang ₁ , Yolanda Mthembu ₂ , Suresh C Regmi ₃ , Jan Holgersson ₂ , Tannin A Schmidt ₄ , Ola Rolfson ₅ , Lena I Björkman ₆ , Martina Sundqvist ₆ , Anna Karlsson-Bengtsson ₇ , Gregory D Jay ₈ , Thomas Eisler ₉ , Roman Krawetz ₁₀ , Niclas G Karlsson ₁

Affiliation

Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada.
Biomedical Engineering Department, University of Connecticut Health Center, Farmington, Connecticut, USA.
Department of Orthopaedics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Chalmers University of Technology, Gothenburg, Sweden.
Department of Emergency Medicine, Warren Alpert Medical School and Division of Biomedical Engineering, School of Engineering, Brown University, Providence, Rhode Island, USA.
Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada.

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.

更新日期：2020-11-21

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