Chondroprotective Effects Of Palmatine On Osteoarthritis In Vivo And In Vitro

Background:In this study we investigated the effect of palmatine (Pal) in a rabbit osteoarthritis (OA) model in vivo and rabbit interleukin-1β (IL-1β)-stimulated chondrocytes in vitro.Methods:Appropriate concentrations of Pal were identified by the MTT assay and used to preincubate IL-1β-induced chondrocytes, as well as an activator or inhibitor of Wnt and Hedgehog signaling pathways. Matrix metalloproteinase (MMP)-1,3and13, tissue inhibitor of metalloproteinase (TIMP)-1, collagenase Ⅱ, aggrecan and the related molecular expressions of Wnt/β-catenin and Hedgehog signaling pathways were investigated. Protein expression was detected by Western blot analysis and messenger RNA (mRNA) expression was examined by real-time reverse transcription polymerase chain reaction (real-time RT-PCR) analysis. Pal was injected into rabbit OA knee joints; histological examination, immunohistochemistry and Mankin scoring of the articular cartilage were performed.Results:Pal (10-100mg/L) had no effect on chondrocyte viability, decreased the expression of MMP-1,3and13, and increased the synthesis of TIMP-1; however, collagenase II and aggrecan were inhibited by IL-1β. When the activator (Licl) and inhibitor (DKK-1) of the Wnt/β-catenin signaling pathway, as well as the inhibitor (cyclopamine) of the Hedgehog signaling pathway were added, the Wnt/β-catenin signaling pathway was less inhibited by Pal, a similar inhibitory effect of the Hedgehog signaling pathway to that of cyclopamine was evident. Additionally, Pal enhanced the effect of cyclopamine. The histological examination, immunohistochemistry and Mankin scoring also demonstrated the protective effect of Pal, and the inhibition of the Wnt and Hedgehog signaling pathways.Conclusion:Pal may be useful in the treatment of OA, in which its effect is likely mediated via the Wnt/β-catenin and Hedgehog signaling pathways.