OBJECTIVE:To explore the molecular mechanism of warming moxibustion(WM) in knee osteoarthritis(KOA).METHODS:The knee joints of 40 New Zealand rabbits were placed in a plaster cast in an extended position to establish a KOA model. The animals were randomly divided into four groups:the control group, model group, WM group, and diclofenac(DF) group. Hematoxylin-eosin staining and the modified Mankin score were applied to evaluate the histopathological changes. Chondrocyte apoptosis was determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) assay. Western blotting and real-time quantitative polymerase chain reaction were performed to measure the expression of interleukin-1β(IL-1β), prostaglandin E receptor 3(PTGER3), a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs-5(ADAMTS-5), matrix metalloproteinase-13(MMP-13), and C-terminal telopeptides of collagen type Ⅱ(CTX-Ⅱ) in cartilage tissues of the different groups. The concentrations of IL-1β, PTGER3, and CTX-Ⅱ in serum were detected by the enzyme-linked immunosorbent assay.RESULTS:Rabbits with KOA in the WM and DF groups showed significantly reduced cartilage erosion and Mankin scores, compared with the untreated rabbits. The number of TUNEL-positive cells observed in the WM group was much fewer than that in the model group. The expression of PTGER3,MMP-13, CTX-Ⅱ, IL-1β, and ADAMTS-5 in cartilage tissues was remarkably downregulated following therapy with WM and DF. Moreover, a marked reduction was observed in the serum levels of IL-1β,PTGER3, and CTX-Ⅱ in the WM and DF groups.CONCLUSION:WM exerts favorable therapeutic effects on articular injuries of KOA by regulating the expression of inflammatory and cartilage degradation-related cytokines.