Treatment of wild-type mice with the transglutaminase inhibitor cystamine limits CIA incidence and progression and osteoclastogenesis. (A) Percentage of mice free from any evidence of macroscopic arthritis in the paws of DBA/1 male mice administered cystamine or vehicle control starting 14 days prior to first CII immunization (n = 10 per treatment group). Data were analyzed by Kaplan-Meier log rank analysis. (B) Median arthritis index analysis. (C) Representative images of knee joint histology from mice harvested at day 42 of CIA. Hematoxylin and eosin (H&E) staining (top panel); trichrome staining (arrows: intact cartilage, middle panel) and TRAP staining for visualizing osteoclasts (arrows, bottom panel). (D) Scatter plot of composite histopathology index analysis of hematoxylin and eosin–stained knee joint sections. Symbols represent composite score for individual mice and bars denote median values for each genotype. Data were analyzed by the Mann-Whitney U test. Quantitative RT-PCR analysis of mRNA levels of RANKL (E), RANKL/OPG ratio (F), and TRAP (G). Data are expressed as average fold change over unchallenged control group; Quantitative RT-PCR analysis of mRNA levels of RANKL (H), ratio of RANKL/OPG (I), and TRAP (J) within the hind paws of otherwise unchallenged mice administered cystamine or vehicle control. Data are representative of 2 independent experiments, presented as mean ± standard error of the mean, and analyzed by the Student t test. Scale bars represent 200 µm (C). *P < .05 Mann-Whitney U test.