OBJECTIVE: β-Catenin is the key mediator of the Wnt signal and also a component of E-cadherin complexes at the intercellular adhering junction, which mediates cell-cell adhesion. We hypothesized that β-catenin might be involved in the long-lasting changed phenotype of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and could play a role in the pathogenesis of RA. In this study we investigated the expression of β-catenin in RA-FLS. METHODS: Synovial tissues were obtained during joint replacement surgery or arthroscopy from six patients with RA, six patients with osteoarthritis (OA), and six patients with joint trauma (Trauma group). Immunohistochemical analysis of β-catenin was performed in the synovial tissues from the three groups. Synovial tissues from three patients in each group were selected at random for FLS isolation. Expression of β-catenin in FLS from the three groups was evaluated at the protein level by western blotting and at the mRNA level by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Immunohistochemistry revealed that the expression of β-catenin in synovial lining cells of the RA samples was significantly greater than that of the OA or trauma samples (p < 0.01). Western blotting and RT-PCR showed that β-catenin expression was elevated in RA-FLS compared with that in OA-FLS or Trauma-FLS (p < 0.05) at the protein level but no difference was found at the mRNA level. CONCLUSIONS: Expression of β-catenin is elevated in RA-FLS, not only in vitro but also in vivo. The increase is due to activation of Wnt/β-catenin signalling. Wnt/β-catenin signalling is activated in RA-FLS, and contributes to the stable activation of RA-FLS.