PPI attenuated collagen induced rheumatoid arthritis and protected bone erosion. CIA mice were treated intragastrically with CMC-Na with or without PPI (10 μg/kg) daily from day 42 after immunization to day 91. All mice were sacrificed on day 91. (A, B) The weight and arthritis swelling severity scores in CIA mice were recorded weekly from day 42 to day 91 after immunization. Data represent mean ± SEM of two pooled experiments, n = 4 for Mock, n = 7 for Model+CMC-Na and n = 7 for Model+PPI group. NS, P > 0.05, *P < 0.05, two-way ANOVA. (C) Representive images of ABOG-staining (4×), micro computed tomography three–dimensional and TRAP staining images (4×) of ankle joints. In micro computed tomography three–dimensional ankle joints, the blue part indicates astragalus, n = 4 for Mock, n = 7 for Model+CMC-Na and n = 6 for Model+PPI group. (D–H) Synovial area in the ankle joint, the cartilage area of the astragalus, the synovial area/astragalus area and astragalus bone volume, and osteoclasts number of the joint were calculated. Data represent mean ± SEM of two pooled experiments, n = 4 for Mock, n = 7 for Model+CMC-Na and 6 for Model+PPI group. *P < 0.05, one-way ANOVA. (I) Double immunofluorescence staining with anti-F4/80 (red) and anti-iNOS (green) antibodies at ankle sections show that decreased activated macrophages (double positive of F4/80 and iNOS) in the synovium of PPI-treated ankle joints, representative images (20×) from the Mock group (n = 4), the Model+CMC-Na (n = 7) and the Model+PPI group (n = 6). (J) Representative images of immunohistochemical staining with anti-CD3 antibody in the synovium around astragalus, bar indicates 50 μm, n = 4 for Mock, n = 7 for Model+CMC-Na and n = 6 for Model+PPI group.