Elimination of uPA or uPAR in DBA/1 mice results in diminished CIA knee joint pathology. (A) Representative hematoxylin and eosin–stained knee joint sections from unchallenged WT and CIA-challenged WT, uPA^−/−, uPAR WT, and uPAR^−/− cohorts. Upon CIA challenge, significant inflammation, synovial hyperplasia, and erosive pannus are apparent in WT mice, whereas knee joints of uPA^−/− and uPAR^−/− mice display markedly attenuated pathological features. Scale bar represents 200 μm. (B) Representative knee joint sections of unchallenged and CIA-challenged WT, uPA^−/−, and uPAR^−/− mice stained by immunohistochemistry for fibrin. Note the fibrin staining along articular surfaces (arrows) and within hyperplastic synovial tissue (asterisk) as CIA-challenged WT mice. Scale bar represents 200 μm. (C) Semiquantitative microscopic analysis of knee joint pathological features from WT (n = 29, red bars) and Plau^−/− (n = 17, white, blue outline bars) mice. Student t test. Scatter plot of composite histopathology index analysis (see Materials and methods) of hematoxylin and eosin–stained knee joint sections. (D) Semiquantitative microscopic analysis of knee joint pathological features from WT (n = 8, red bars) and Plaur^−/− (n = 16, white, green outline bars) mice. Student t test. Scatter plot of composite histopathology index analysis (see Materials and methods) of hematoxylin and eosin–stained knee joint sections. Each symbol represents the composite score for individual knees and bars denote median values for each genotype. P values were determined by Mann-Whitney U test. #P < .001 and *P < .05.