Hinokitiol reduces matrix metalloproteinase expression by inhibiting Wnt/β-Catenin signaling in vitro and in vivo

•Hinokitiol inhibits the IL-1β and Licl -induced expression of MMPs in chondrocytes.•The in vitro results indicate that hinokitiol could inhibit Wnt/β-catenin pathway.•We find the inhibitory effect of hinokitiol is weaker than that of Dkk-1.•The in vivo results show that hinokitiol could delay the progression of OA.•The study suggests hinokitiol could be a promising therapeutic agent for the OA.

ObjectiveIn this study, we investigated the effects of hinokitiol on matrix metalloproteinase (MMP)-1, -3, -13, collagen type II (Col2a1) and β-catenin expressions in rat chondrocytes induced by interleukin-1β and in an experimental rat model induced by intra-articular injection of mono-iodoacetate (MIA) into the knee.MethodsChondrocytes were cultured from the articular cartilage of 2-week-old rats. Passaged chondrocytes were pretreated with hinokitiol for 2 h followed by co-incubation with IL-1β for 24 h. Quantitative real-time polymerase chain reaction and Western blotting were used to assess the expression of MMP-1, -3, -13, Col2a1 and β-catenin. Chondrocytes were also treated with Licl, Dickkopf-1, and/or hinokitiol for 24 h, the MMP-1, -3, -13 and β-catenin protein levels determined by Western blotting. The in vivo effects of hinokitiol were assessed by morphological and histological analyses following MIA injection.ResultsHinokitiol inhibited IL-1β-stimulated MMP-1,-3 and -13 expressions and IL-1β-induced activation of intracellular β-catenin proteins in cultured chondrocytes. In vivo, morphological and histological examinations demonstrated that hinokitiol significantly ameliorated cartilage degeneration.ConclusionsHinokitiol is an effective anti-inflammatory reagent that acts by inhibiting the Wnt/β-catenin signaling pathway and could be a promising therapeutic agent for the prevention and treatment of osteoarthritis.