N‐Glycan profiling of chondrocytes and fibroblast‐like synoviocytes: Towards functional glycomics in osteoarthritis

PURPOSE: N‐Glycan profiling provides an indicator of the cellular potential for functional pairing with tissue lectins. Following the discovery of galectin expression by chondrocytes as a factor in osteoarthritis pathobiology, mapping of N‐glycans upon their phenotypic dedifferentiation in culture and in fibroblast‐like synoviocytes is a step to better understand glycobiological contributions to disease progression. EXPERIMENTAL DESIGN: The profiles of cellular N‐glycans of human osteoarthritic chondrocytes and fibroblast‐like synoviocytes were characterized by mass spectrometry. RT‐qPCR experiments determined mRNA levels of 16 glycosyltransferases. Responsiveness of cells to galectins was quantified by measuring the mRNA level for interleukin‐1β. RESULTS: The shift of chondrocytes to a fibroblastic phenotype (dedifferentiation) is associated with changes in N‐glycosylation. The N‐glycan profile of chondrocytes at passage 4 reflects characteristics of synoviocytes. Galectins‐1 and ‐3 enhance expression of interleukin‐1β mRNA in both cell types, most pronounced in primary culture. Presence of interleukin‐1β leads to changes in sialylation in synoviocytes that favor galectin binding. CONCLUSIONS AND CLINICAL RELEVANCE: N‐Glycosylation reflects phenotypic changes of osteoarthritic cells in vitro. Like chondrocytes, fibroblast‐like synoviocytes express N‐glycans that are suited to bind galectins, and these proteins serve as inducers of pro‐inflammatory markers in these cells. Synoviocytes can thus contribute to disease progression in osteoarthritis in situ.