In hTNFtg mice, synovial inflammation increased over time (0.025 mm2 at week 2 versus 0.65 mm2 at week 14; P < 0.05), with the most prominent increase between weeks 4 and 6 (0.029 mm2 and 0.78 mm2, respectively; P < 0.05). Loss of cartilage was seen only between weeks 2 and 4. After week 4, the cartilage area and thickness remained stable, arguing for a dissociation between cartilage degradation and pannus formation. As seen in toluidin-blue staining, a loss of proteoglycans occurred over time, which started at week 4 and peaked at week 8. There was a prominent attachment of pannus tissue to articular cartilage. Attachment started after week 4, peaked at week 10 and showed a decrease thereafter. This observation was supported by in vitro attachment data showing that early moderate loss of proteoglycans (as induced by 1 ng/ml IL-1) strongly enhanced attachment of synovial fibroblasts while an almost complete loss of proteoglycans (as induced by 10 ng/ml IL-1) did not facilitate fibroblast attachment.