(A) Scheme of RS-504393 treatment at different DMM-induced OA stages. (B) OARSI scoring (N=6 for each of the experimental points described) was measured from sections from DMM/sham knees at 8 and 12 weeks after surgery with or without RS-504393 treatment at the time indicated and (C) representative sections are shown at each time point (scale bars 100 µm). (D) Osteophyte size scoring was measured from sections (4/mouse) obtained from the anterior/medial margin of the tibia from DMM/sham knees at 8 weeks (N=6 for both untreated and RS-504393 treated samples) and 12 weeks after surgery (for untreated samples, N=5 for Sham and N=4 for DMM; for samples RS-504393 treated from 1–4wks, N=5 for Sham and N=6 for DMM; for samples RS-504393 treated from 4–8wks, N=6 for Sham and N=3 for DMM), with or without RS-504393 treatment at the time indicated. (E) Longitudinal pain measures were obtained by assessing the weight shift from the operated (right) limb to the un-operated (left) limb, in mice at 2, 4, 8 and 12wks after DMM/sham surgery, with or without RS-504393 treatment at the time indicated using the Incapacitance meter (N=6 for each of the experimental points described). All graphs represent the mean ± standard deviation. Significance was set at P < 0.05.