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Sci Rep. 2016 May 9;6:25463. doi: 10.1038/srep25463.

Galectin-3 Binds to Lubricin and Reinforces the Lubricating Boundary Layer of Articular Cartilage.

Author information

1
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States of America.
2
Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, United States of America.
3
School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY, United States of America.
4
Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, United States of America.

Abstract

Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. Extensive O-linked glycosylation within lubricin's mucin-rich domain is critical for its boundary lubricating function; however, it is unknown exactly how glycosylation facilitates cartilage lubrication. Here, we find that the lubricin glycome is enriched with terminal β-galactosides, known binding partners for a family of multivalent lectins called galectins. Of the galectin family members present in synovial fluid, we find that galectin-3 is a specific, high-affinity binding partner for lubricin. Considering the known ability of galectin-3 to crosslink glycoproteins, we hypothesized that galectins could augment lubrication via biomechanical stabilization of the lubricin boundary layer. We find that competitive inhibition of galectin binding results in lubricin loss from the cartilage surface, and addition of multimeric galectin-3 enhances cartilage lubrication. We also find that galectin-3 has low affinity for the surface layer of osteoarthritic cartilage and has reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions. Together, our results suggest that galectin-3 reinforces the lubricin boundary layer; which, in turn, enhances cartilage lubrication and may delay the onset and progression of arthritis.

PMID:
27157803
PMCID:
PMC4860590
DOI:
10.1038/srep25463
[Indexed for MEDLINE]
Free PMC Article

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