IL-1beta and TNF-alpha alter the glycophenotype of primary human chondrocytes in vitro

Despite the significance of glycoproteins for extracellular matrix assembly in cartilage tissue, little is known about the regulation of the chondrocyte glycophenotype under inflammatory conditions. The present study aimed to assess the effect of IL-1beta and TNF-alpha on specific features of the glycophenotype of primary human chondrocytes in vitro. Using LC-MS, we found that both cytokines increased overall sialylation of N- and O-glycans and induced a shift towards alpha-(2-->3)-linked sialic acid residues in chondrocyte glycoproteins. These results were supported by quantitative PCR showing increased expression of alpha-(2-->3) sialyltransferases in treated cells. Moreover, we found that both IL-1beta and TNF-alpha induced a considerable shift from oligomannosidic glycans towards complex-type N-glycans. In contrast, core alpha-(1-->6)-fucosylation of chondrocyte N-glycans was found to be reduced particularly by TNF-alpha. In summary, inflammatory conditions induce specific alterations of the chondrocyte glycophenotype which might affect cell-matrix interactions or the function of endogenous lectins.