Paeonol Ameliorates Inflammation and Cartilage of Chondrocytes in Osteoarthritis by Upregulating SIRT1

Abstract

Objective: To explore the possible role of paeonol on chondrocyte inflammation and cartilage protection in osteoarthritis (OA).Methods: Primary chondrocytes were isolated from rat stifle joints, and were identified through toluidine blue staining and immunofluorescence staining of type II collagen. The chondrocytes were transfected with sh-SIRT1 or/and paeonol (0, 20, 50, 100, 200, 1000 mg/L) before OA modeling induced by IL-1β. ELISA determined the expressions of TNF-α, IL-17 and IL-6, and apoptotic rate was examined by flow cytometry. qRT-PCR and Western blot quantified the expressions of MMP-1, MMP-3, MMP-13, TIMP-1, cleaved-caspase-3, Bax, Bcl-2, and the proteins related to NF-κB pathway.Results: Increases in TNF-α, IL-17, IL-6, MMP-1, MMP-3 and MMP-13 and decrease in TIMP-1 were found in IL-1β stimulated chondrocytes. The apoptotic rate as well as the expressions of cleaved-caspase-3 and Bax was up-regulated, and Bcl-2 expression was suppressed in response to IL-1β treatment. NF-κB pathway was activated in IL-1β-stimulated chondrocytes. Paeonol enhanced SIRT1 expression to inactivate NF-κB pathway, thus ameliorating the secretion of inflammatory cytokines, extracellular matrix degradation and chondrocyte apoptosis.Conclusion: Paeonol inhibits IL-1β induced inflammation and extracellular matrix degradation in chondrocytes through up-regulating SIRT1 and suppressing NF-κB pathway.