Fig. 4

Intra-articular collagenase injection attracts human tumor necrosis factor–transgenic (hTNFtg) synovial fibroblasts (SFs) into knee joints. a–d Wild-type mice received simultaneous intra-articular injections of (a) PBS into the left and (b) bacterial collagenase into the right knee joints. c and d After 48 h, quantification of toluidine blue staining showed a significant proteoglycan loss (arrows) without affecting the total cartilage area. Scale bar = 400 μm, n = 4. e and f Subsequent intravenous injection of 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide–labeled hTNFtg SFs showed increased fluorescence intensity in the collagenase-pretreated right knee joint in comparison to the control left knee joint (n = 5). The values represent the mean ± SEM. * p < 0.05, ** p < 0.01. Cy.7 Cyanine 7