Figure 3.
Inhibition of the activation of VEGFR2 decreases the expression of MMP13 and RUNX2 during OA development and progression. Immunofluorescence (IF) assays were done in histological sections of cartilage tissues in mice at 12 weeks after partial medial meniscectomy (PMM). IA injection of pazopanib (Paz) or vandetanib (Van) or vehicle (Veh, 5% DMSO in PBS) was performed at week 1 (Gp1, inflammatory pain stage), week 4 (Gp2, early OA stage) or week 8 (Gp3, advanced OA stage) after PMM, twice per week for 12 weeks. Levels of MMP13 (green), RUNX2 (red), pVEGFR1 (green) and pVEGFR2 (red) were examined in knee cartilage by IF microscopy (A). Quantitative analysis results for MMP13, RUNX2, pVEGFR1 and pVEGFR2 expression (n=3) (B-M). Statistical analysis was conducted using one-way ANOVA followed by the Tukey-Kramer test. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 making comparisons between groups with or without pazopanib or vandetanib treatment in mice with PMM. 4′,6-diamidino-2-phenylindole (DAPI) stains nuclei blue. Scale bars: 100 μm.