Figure 3

Pre-emptive cordycepin treatment reduces pain and synovial inflammation in the MIA model of OA. OA was induced on day 0 by injecting MIA (1 mg/50 µl) in the left knee joints of male Sprague Dawley rats (A,B). Cordycepin (Cordy; 8 mg/kg, orally, every other day) or vehicle (Veh) was administered for a period of 2 weeks, starting at day 0 until day 14. Saline (50 µl) injected rats were used as controls. Cordycepin treatment reduced MIA-induced changes in pain behaviour measured as weightbearing asymmetry (A) and mechanical allodynia (B). Cordycepin treatment reduced MIA-induced increase in synovial macrophages (C,G), cellularity/lining thickness (D,G), cell proliferation (E,H) and angiogenesis (F and H). Immunostaining of CD68 positive macrophages and haematoxylin and eosin stained sections showed cellular infiltration (G). Immunostained sections for proliferating endothelial cells (ECs) (proliferating cell nuclear antigen [PCNA] positive CD31 cells); black arrows, non-proliferating ECs; blue arrows and PCNA positive cells; red arrows (H). Data are presented graphically as mean ± SEM from n = 10 rats/group. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 versus vehicle-treated saline-injected controls. ⁺p < 0.05, ⁺⁺p < 0.01, ⁺⁺⁺p < 0.001, ⁺⁺⁺p < 0.0001 versus vehicle-treated MIA-injected day 14 OA rats.