Synovial cells of the joint play a key role in the progression of rheumatoid arthritis (RA). However, the mechanism(s) that triggers aggression of RA synovial cells but not other arthropathies such as osteoarthritis (OA) is not clear. Here we examined expression of WNT and the WNT inhibitor, secreted frizzled-related protein (FRP), in RA and OA synovium by reverse transcription-PCR. WNT10B was most frequently detected in RA synovium, and FRP1, FRP2, and FRP4 in OA synovium. Immunohistochemistry localized WNT10B and FRP1 in synovial lining cells, fibroblasts, and endothelial cells in RA and OA synovium, respectively, and WNT10B expression was increased in parallel with the degree of inflammatory cell infiltration and tissue fibrosis. Membrane-type 1 matrix metalloprotemse (MT1MMP) was upregulated by WNT10B and activation of WNT signaling. MT1MMP immunolocalized to cells identical to WNT10B and P-catenin staining. The present study demonstrated that WNTs and FRPs are differentially expressed in RA and OA synovium, and suggests an involvement in the pathology of these diseases. (c) 2006 Elsevier Inc. All rights reserved.