Histopathological analysis of the knee joints 2 weeks after needle injury. Unpunctured control joints of F8^−/− mice (A) and severe thickening of the synovium with inflammation in the punctured, but untreated, joints of F8^−/− animals (B). Representative hematoxylin and eosin–stained sections of joints from needle-punctured F8^−/− animals treated with the anti–TNF-α biologic etanercept (C) or from F8^−/−TNF-α^−/− (D) or F8^−/−iRhom2^−/− mice (E). (F) Evaluation of synovitis using a modified Krenn score indicated high levels in untreated needle-punctured F8^−/− mice (8.5 ± 0.2; n = 6), with significantly reduced levels in etanercept-treated F8^−/− mice (5.3 ± 1.4; n = 7), F8^−/−/TNF-α^−/− mice (6.8 ± 0.6 n = 6), and F8^−/−/ iRhom2^−/− mice (6.2 ± 0.4; n = 9). The images shown are representative for the average synovial inflammation observed in each treatment group; yellow arrows denote the analyzed synovial area. Scale bars, 100 µm. Please see supplemental Figure 1 for details. *P < .05 vs untreated F8^−/− mice. F, femur; m, meniscus; T, tibia.