(A) To assess the inflammatory signature of joints of obese mice supplemented with oligofructose or cellulose, MCP-1 and Tnf expression was examined. MCP-1 was detected via immunofluorescence, with DAPI counterstaining of nuclei. The blue dotted lines outline articular cartilage on the femoral condyle (F, femur), the yellow dotted lines demarcate the margins of the synovial membrane, and the white scale bar represents 50 µm. Tnf expression was assessed via IHC, with synovial staining identified with red arrows and black scale bars representing 200 µm (M, meniscus; T, tibia). (B) To evaluate articular chondrocyte hypertrophic differentiation and cartilage matrix changes, Runx2, Mmp13, and Col10 expression was examined via IHC, with yellow dotted lines demarcating the tidemarks, red arrows pointing to chondrocytes or areas with positive staining, and black scale bars representing 50 µm (M, meniscus; T, tibia; F, femur). (C) Representative Safranin O/Fast Green–stained sections depict posterior medial joint margins with an osteophyte identified by a yellow asterisk in the obese-DMM-cellulose group and the black scale bar representing 200 µm (M, meniscus; T, tibia). (D) MicroCT imaging reveals mineralized structures in experimental joints, with mineralized menisci identified with white arrows and the white scale bar representing 1 mm. (E) Amira-based reconstruction of the raw dicoms from the microCT imaging was performed to enable quantitative segmentation of calcified menisci colored white with the white scale bar representing 1 mm. (F) Histology sections similar to those shown in C were used to quantify the number of osteophytes per histologic section in each experimental group. Data represent the group mean (± SEM), each symbol represents the average number of osteophytes per section from 3 levels within a joint (n = 5–7 joints), and the black dotted line represents the average in the lean-sham-cellulose negative control group. (G) Amira reconstructions similar to those depicted in E were used to quantify the volume of calcified meniscus in various experimental groups. Data represent the group mean (± SEM), each symbol represents the average calcified meniscus volume from each joint (n = 4 joints), and the black dotted line represents the average in the lean-sham-cellulose negative control group. Significant differences between groups in F and G were identified via 2-way ANOVA with a Tukey multiple comparison post-test (P values for the obesity effect are reported).