〔Abstract〕 Objective To observe the effect of different synovial cell secretions on chondrocytes after LPS-induced inflammation, and to explore the mechanism of two synovial cell secretions causing cartilage damage in the progression of KOA disease. Methods Two kinds of synovial cells were co-cultured at 1∶4 and LPS-induced inflammation. The supernatant and exocrine were extracted, and then the normal and LPS-induced inflammation were extracted. The human cartilage tissue obtained during the operation was isolated and cultured into chondrocytes, which were divided into five groups: the first group was added with FLS secretion, the second group was added with normal FLS secretion, the third group was added with secretion after co-culture of two kinds of synovial cells, the fourth group was added with inflammatory MLS secretion, and the fifth group was added with inflammatory FLS secretion. CCK-8 was used to detect the viability of chondrocytes in each group. TNF-α,IL-1β,IL-6 level in the supernatant of chondrocytes in each group was detected by ELISA. The protein expression of TLR4,NF-κB,IkK,IκB,ADAMTS5 in chondrocytes of each group was detected by Western blot method.Results CCK-8 showed that the activity of chondrocytes in the three groups of inflammatory secretions decreased compared with the secretions from normal synovial cells(P<0.05); ELISA showed TNF-α,IL-1β,IL-6 level in the supernatant of group Ⅲ, IV and V was higher than that of group Ⅰ and Ⅱ(P<0.05), TNF-α,IL-1β,IL-6 level in group Ⅲ was higher than that in group IV but lower than that in group V(P<0.05). Western blot showed the protein expression of TLR4,NF-κB,IkK,IκB,ADAMTS5 in chondrocytes of group Ⅲ, Ⅳ and Ⅴ was higher than that in group Ⅰ and Ⅱ(P<0. 05),the protein expression of TLR4,NF-κB,IkK,IκB,ADAMTS5 in group Ⅲ was higher than that in group Ⅳbut lower than that in group Ⅴ(P<0.05).Conclusion Two kinds of synovial cell-derived secretions after LPSinduced inflammation can regulate cartilage TLRs/NF-κB signal pathway, causing cartilage inflammation. The inflammatory effect of MLS secretion is stronger than that of FLS secretion, but the inflammatory effect of MLS secretion under two co-cultures is weaker than that of MLS secretion alone.