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

Abstract

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 Nglycans that are suited to bind galectins, and these proteins serve as inducers of proinflammatory markers in these cells. Synoviocytes can thus contribute to disease progression in osteoarthritis in situ.

Mass spectrometry imaging spatially identifies complex-type N-glycans as putative cartilage degradation markers in human knee osteoarthritis tissue

“…Based on these findings, it can be postulated that galectins could be present in OA cartilage as on-site effectors that can translate the sugar code of cells and matrix into biological functions. Fuehrer et al [ 33 ] also hypothesized that N -glycosylation could reflect phenotypic changes in osteoarthritic cells in vitro. Like chondrocytes, fibroblast-like synoviocytes express N -glycans that are suited to bind galectins-1 and -3, and these proteins serve as inducers of pro-inflammatory markers, such as interleukin-1β [ 33 ].…”

“…Fuehrer et al [ 33 ] also hypothesized that N -glycosylation could reflect phenotypic changes in osteoarthritic cells in vitro. Like chondrocytes, fibroblast-like synoviocytes express N -glycans that are suited to bind galectins-1 and -3, and these proteins serve as inducers of pro-inflammatory markers, such as interleukin-1β [ 33 ]. This data suggests there is a potential role for lectins to selectively manipulate glycoprotein function in OA disease.…”

Characterization of aberrant glycosylation associated with osteoarthritis based on integrated glycomics methods

“…It is known that the alterations in glycosylation contribute to the process of diseases. A recent study reported that alterations in glycosylation reflected phenotypic changes in osteoarthritic cells [ 28 ]. For instance, the aberrant of high mannose-type N-glycans was observed in human and mouse OA cartilage, which is correlated with the release of MMP-13 and ADAMTS-5 in degraded cartilage [ 29 ].…”

Iridoid from Eucommia ulmoides Oliv. Exerts Antiarthritis Effects by Inhibiting the JAK2/STAT3 Signaling Pathway In Vivo and In Vitro

“…TNF- α mainly causes cartilage damage in RA by promoting the release of various inflammatory mediators, the degradation of cartilage proteoglycan, and the expression of vascular endothelial cell adhesion molecules [ 30 ]. In rheumatoid arthritis, the chronic inflammation of synovial cells is largely caused by IL-1 β overproduction; this directly activates FLS and leads to joint destruction and bone resorption [ 31 , 32 ]. One of the most significant pro-inflammatory factors in the course of many inflammatory reactions is IL-6.…”