Figure 4.

Therapeutically administered cordycepin reduces MIA-induced pain and synovial inflammation. OA was induced on day 0 by injecting MIA (1 mg/50 µl) in the left knee joints. Cordycepin (Cordy; 8 mg/kg, orally, every other day) or vehicle (Veh) was administered for a period of 2 weeks starting at day 14; once MIA-induced changes were established, to day 28. 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). Synovial sections were immunostaining for CD68 positive macrophages, PCNA positive CD31 blood vessels and 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 (C). Haematoxylin and eosin stained sections showed cellular infiltration (C). MIA-induced synovial inflammation measured as macrophage fractional area (D) and synovial lining thickness score (E) as well as synovial cell proliferation (F) were also reduced in the cordycepin treated groups. Cordycepin treatment did not significantly reduce MIA-induced synovial angiogenesis (G). Immunofluorescence staining for synovial NFκB (p65) intensity (H,I) showed that synovial macrophages expressed NFκB and the expression of NFκB increased with MIA-induced disease progression (H). Cordycepin treatment reduced the synovial NFκB (p65) intensity (I). Scale bars are 100 µm. Data are mean ± SEM of n = 10 rats per 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 versus vehicle-treated MIA-injected OA rats at day 28. ^##p < 0.01 versus MIA-injected OA rats at day 14.