Fibrin deposition on cartilage correlates with the severity of cartilage damage in human and experimental RA. (a) Knee arthroscopy of an end-stage RA patient displays synovitis with goden shimmering deposits (white arrows), and vis-à-vis round plaques appearing on cartilage (black arrows). Scale bar = 200 μm. n = 4. (b) Immunohistochemistry showed fibrin(ogen) deposits on both synovium and cartilage. Scale bar = 30 μm. n = 4. (c) Graph shows fibrin deposit scores (arbitrary unit = AU) in low, medium, and high damaged areas of cartilage from 4 RA patients. For each level of cartilage degradation, one dot corresponds to one of the 4 patients. n = 4. One-way ANOVA post hoc Bonferroni correction. *p < 0.05, **p < 0.01, ***p < 0.001. (d) Representative immunohistochemical staining for fibrin deposits in WT and Fg−/− murine knees with AIA and representative Safranin-O histologies for cartilage damage and synovial thickness on consecutive sections. Black arrows show cartilage damage and fibrin deposits in WT knees. White arrows show recess occlusion in WT knees. Red arrows show synovial thickness. Scale bars for 40x = 300 μm and 200x = 120 μm. WT = 8, Fg−/− = 8. (e) Score for fibrin deposition and for (f) cartilage damage and synovial thinckness in WT and Fg−/− knees. WT = 8, Fg−/− = 8. (g) Correlation graph between fibrin deposit score (AU) and cartilage damage score (AU). Linear regression and Pearson correlation tests. **p < 0.01. (h) qRT-PCR of the indicated genes in murine chondrocytes stimulated for 4 h with 500 ug/ml Fg. Two-way ANOVA post hoc Bonferroni correction. n = 3 experiments. **p < 0.01, ****p < 0.0001.