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

OBJECTIVE

In 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.

METHODS

Chondrocytes were cultured from the articular cartilage of 2-week-old rats. Passaged chondrocytes were pretreated with hinokitiol for 2h followed by co-incubation with IL-1β for 24h. 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 24h, 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.

RESULTS

Hinokitiol 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.

CONCLUSIONS

Hinokitiol 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.