Fig. 2

Fap promotes OA progression in a mouse DMM model. a–c Safranin O/Fast Green staining in control and Fap KO mice treated with FAPi or vehicle after DMM surgery. Weekly intra-articular administration of FAPi (40 μg/kg body weight) or vehicle (PBS) in 10-week-old mice was started 3 days after the surgery and continued for 8 weeks before paraffin sectioning and safranin O/fast green staining of the knee joints. Representative cartilage erosion (a, top: femur, bottom: tibia), subchondral bone thickening (b) and synovitis (c) images are shown (n = 6–7 mice per genotype in each treatment group). Yellow dotted lines indicate the subchondral bone plate. Arrows indicate the synovium. Scale bars: 100 μm. d–f Quantification of the OARSI score (d), subchondral bone thickness (e) and synovitis score (f). OARSI scores were calculated based on the erosion of the medial tibial plateau cartilage (a, bottom). Subchondral bone thickness was measured as the mean distance of five evenly distributed measuring points between the lower edge of the articular cartilage and the roof of the cancellous bone. Synovitis scores were calculated by summing the enlargement of the synovial lining cell layer, density of the resident cells and inflammatory infiltration. g, h Immunostaining of Col II in the knee joints (g) with quantifications (h) (n = 6 mice per genotype in each treatment group). DAPI staining indicates the nucleus. Scale bars: 100 μm. The statistical significance was assessed using two-way ANOVAs with Sidak’s multiple comparison tests. Data are presented as the mean ± SD (*P < 0.05, **P < 0.01, ***P < 0.001)