Combinatorial therapy and PRG4 monotherapy preserve articular cartilage at early and late time points in a mild-to-moderate model of posttraumatic OA. Joints were collected and analyzed at 2.5- and 3.5-months after DMM surgery by phase-contrast microCT. (A) Representative images of joints at 3.5-months post-surgery that show the medial compartment (femur + tibia) from each experimental group. Red volumes represent articular cartilage. (B) Cartilage volume is maintained in all groups at the 2.5-month time point; however, significant volume loss in cartilage has occurred in the IL-1Ra and untreated groups by 3.5 months. (C) At 2.5 months the untreated group has begun to lose covered surface area when compared to sham; however, by 3.5 months the untreated group has lost significantly more than the sham-treated group, combinatorial-treated, and PRG4-treated groups, with IL-1Ra-treated animals trending toward a reduction in surface area. Data are represented by min-to-max box and whisker plots. n = 6 (3.5 months; all groups); n = 3 (2.5 months; combinatorial, PRG4) and 4 (2.5 months; IL-1Ra, empty, and sham). *p < 0.05 ANOVA. Scale bar, 1mm. DMM, destabilization of the medial meniscus.