Early continuous Gβγ-GRK2 inhibition switches synovial macrophage phenotype to M2 in early-stage PTOA. (A) Schematic representation of timeline of drug treatment after sham (n = 5) or DMM surgeries. Two days before surgery, mice started receiving daily intraperitoneal injections of vehicle (V; n = 10), gallein (G; 10 mg/kg per day, n = 10), paroxetine (Px; 5 mg/kg per day, n = 7), fluoxetine (Fx; 5 mg/kg per day, n = 9), or indomethacin (Indo; 2.5 mg/kg per day, n = 9). All mice were euthanized 1 week after surgery. Green arrows denote the duration of drug treatment. Representative images of IF staining of (M1 markers) (B) iNOS, (D) CD80, and (F) CD163 (M2 marker) in the in the anterior femoral synovium of sham and DMM mouse knee sections 1 week after DMM or sham surgery. Target proteins are represented in red. DAPI (blue) stains nuclei; scale bar, 50 µm. Quantification of the percentage of positive cells expressing (C) iNOS, (E) CD80, and (G) CD163. n = 5 per group; * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001 vs. DMM + V group using one-way ANOVA. Values are expressed as means ± SEM.