| Autor: |
Sarah A, Flowers, Kristina A, Thomsson, Liaqat, Ali, Shan, Huang, Yolanda, Mthembu, Suresh C, Regmi, Jan, Holgersson, Tannin A, Schmidt, Ola, Rolfson, Lena I, Björkman, Martina, Sundqvist, Anna, Karlsson-Bengtsson, Gregory D, Jay, Thomas, Eisler, Roman, Krawetz, Niclas G, Karlsson |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
J Biol Chem |
| ISSN: |
1083-351X |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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