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bioRxiv · 10.1101/2019.12.20.884148

Core-2 O-glycans are required for Galectin-3 interaction with the osteoarthritis related protein lubricin

Flowers, S. A.·Thomsson, K. A.·Ali, L.·Huang, S.·Mthembu, Y.·Regmi, S. C.·Holgersson, J.·Schimdt, T. A.·Rolfson, O.·Bjorkman, L. I.·Sundqvist, M.·Karlsson, A.·Jay, G. D.·Eisler, T.·Krawetz, R.·Karlsson, N. G.
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Abstract

Synovial fluid lubricin (proteoglycan 4) is a mucin-type O-linked glycosylated (60% of the mass) biological lubricant involved in osteoarthritis (OA) development. Lubricin has been reported to be cross-linked by synovial galectin-3 on the lubricating articular surface. Here, we confirm that binding to galectin-3 depended on core-2 O-linked glycans, where surface plasmon resonance of a recombinant lubricin (rhPRG4) devoid of core-2 structures lacked binding capacity to recombinant galectin-3. Both galectin-3 levels and interactions with synovial lubricin were found to be decreased in late-stage OA patients coinciding with an increase of truncated and less sialylated core 1 O-glycans. These data suggest a defect cross-linking of surface active molecules in OA and provides novel insights into OA molecular pathology.

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Flowers, S. A., Thomsson, K. A., Ali, L., Huang, S., Mthembu, Y., Regmi, S. C., Holgersson, J., Schimdt, T. A., Rolfson, O., Bjorkman, L. I., Sundqvist, M., Karlsson, A., Jay, G. D., Eisler, T., Krawetz, R., Karlsson, N. G.. 2019-12-21. Core-2 O-glycans are required for Galectin-3 interaction with the osteoarthritis related protein lubricin. https://doi.org/10.1101/2019.12.20.884148

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