AbstractObjectiveRheumatoid arthritis (RA) is a chronic inflammatory disease that is characterized by hypertrophy of the synovial tissue, leukocyte infiltration, angiogenesis, and ultimately joint destruction. Mucins (MUCs) are a family of heavily glycosylated proteins that protect epithelial membranes and are used as ligands for cell adhesion. MUC gene expression has been found to be altered in many cancers and inflammatory states. This study was undertaken to examine its expression in synovial tissue (ST) and role in arthritis.MethodsWe performed immunohistochemistry, Western blotting, and reverse transcriptase–polymerase chain reaction to determine expression patterns of MUC1, MUC2, MUC3, and MUC5AC in RA, osteoarthritic (OA), and normal human ST.ResultsMUC3 was expressed in synovial lining cells, macrophages, and fibroblasts. Significantly more RA (n = 12) and OA (n = 13) synovial lining cells expressed MUC3 than did normal synovial lining cells (n = 7) (22% and 24% versus 0.4%, respectively; P < 0.05). Additionally, macrophages in RA and OA ST expressed significantly more MUC3 than did macrophages in normal ST (50% and 51% versus 10%, respectively; P < 0.05). MUC5AC was expressed at low levels in synovial lining cells, macrophages, and endothelial cells in RA and OA ST, and was barely expressed in normal ST. MUC1 and MUC2 proteins were not detected in ST. Messenger RNA (mRNA) for MUC3 and MUC5AC was detected in ST, and mRNA for MUC3 was detected in cultured ST fibroblasts.ConclusionThese data demonstrate up‐regulated MUC expression by ST cells and suggest a novel role of MUC3 and MUC5AC in the pathogenesis of arthritis.