Understanding the mechanisms that cause synovial fibroblast to degrade the extracellular matrix (ECM) in arthritic joints is key. In cancer, hyper O-glycosylation of cell-surface proteins leads to ECM degradation by cancer cells. This process is activated by the relocation of N-acetylgalactosaminyltransferases (GALNTs) from the Golgi to the endoplasmic reticulum (ER). This relocation is known as GALNT activation (GALA) and promotes high O-glycosylation and the synthesis of the Tn glycan. A study in Nature Communications investigates whether the GALA pathway is altered in synovial fibroblasts in arthritic joints.
Using the collagen antibody-induced arthritis (CAIA) mouse model of RA, the authors found that, similarly to humans, GALNT relocation and Tn glycan levels were increased in mice with CAIA compared with control animals. In both humans and mice, synovial-lining fibroblasts were identified as the cells that had high GALNT relocation and expression of Tn glycan. In synovial fibroblast from individuals with osteoarthritis and RA, exposure to ECM proteins activates the GALA pathway, whereas cells from healthy individuals had little or no response.
