Complex-Type N -Glycans Are Associated with Cartilage Degeneration within Different Loading Sites of the Tibial Plateau for Knee Osteoarthritis Patients.

Abnormal N -glycosylation has been shown to play an important role in the pathogenesis of multiple diseases. However, little is known about the relationship between N -glycosylation and knee osteoarthritis (KOA) progression at the tissue level. Thus, the aim of this study was to quantify the cartilage histomorphometric changes in formalin-fixed paraffin-embedded (FFPE) tissue collected from the lateral and medial compartments of the tibial plateau KOA patients ( n = 8). Subsequently, N -glycans were analyzed by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) followed by in situ MS/MS fragmentation. Overall, the Osteoarthritis Research Society International (OARSI) histological grade and cartilage surface fibrillation index were significantly higher, and chondrocyte size in the superficial zone was much larger, for the medial high-loaded cartilage compared to the lateral less-loaded cartilage. Among 92 putative N -glycans observed by MALDI-MSI, 3 complex-type N -glycans, (Hex) 4 (HexNAc) 3 , (Hex) 4 (HexNAc) 4 , and (Hex) 5 (HexNAc) 4 , and 1 oligomannose-type N -glycan, (Hex) 9 (HexNAc) 2 , were significantly higher in intensity in the medial cartilage compared to the lateral cartilage, whereas 2 tetra-antennary fucosylated-type N -glycans, (Hex) 3 (HexNAc) 6 (Fuc) 2 and (Hex) 3 (HexNAc) 6 (Fuc) 3 , were significantly higher in intensity in the lateral cartilage than the medial cartilage. Our findings indicate that complex-type N -glycans are associated with higher severity of cartilage degeneration and may influence the cellular processes of KOA.