(A) Schematic of study design. (B) In the pretreatment group of animals, mBSA injection into the knee significantly induced joint swelling on days 1, 4, 6, and 7 compared with PBS, and B1R blockade significantly reduced knee circumference induced by mBSA on days 1, 2, 4, and 6. n = number of knees per group: PBS, n = 8; vehicle, n = 12; SSR, n = 14. (C) No significant changes in IL-1β and MCP-1/CCL2 were found in knee homogenates among groups. (D) In the treatment group of animals, mBSA injection into the knee significantly induced joint swelling on days 1, 4, and 6 compared with PBS, and B1R blockade significantly reduced knee circumference induced by mBSA on days 1, 2, 4, 6, and 7. n = number of knees per group: PBS, n = 8; vehicle, n = 12; SSR, n = 14. (E) Significant reduction in IL-1β and MCP-1/CCL2 was found in knee homogenates from SSR-treated animals compared with vehicle-treated ones. (F) Representative 3D μCT reconstructions of murine knee joints. Arrowheads indicate sites of cortical bone erosion. (G) Qualitative scoring of cortical bone erosion demonstrates amelioration of mBSA-induced cortical destruction in SSR240612-treated mice. n = number of knees per group: healthy control, n = 7; PBS n = 4; pretreatment vehicle, n = 6; pretreatment SSR, n = 7; treatment vehicle, n = 6; treatment SSR, n = 7. (H and I) Analysis of the epiphyseal and metaphyseal cortical tissue mineral density (Ct.TMD), trabecular tissue mineral density (Tb.TMD), and mean trabecular thickness (Tb.Th) showed catabolic bone remodeling in all mBSA-treated mice relative to healthy control, and significant inhibition of mBSA-induced cortical and trabecular bone loss in SSR240612-treated groups. HA, hydroxyapatite. Results are expressed as mean ± SD. *P < 0.05 vs. SSR, #P < 0.05 vs. PBS (B and D). *P < 0.05, #P < 0.05 vs. control (E, G–I). Significance was determined by 2-way ANOVA (B and D), Kruskal-Wallis test (C, E, and G), and 1-way ANOVA (H and I).