Attenuation of osteoarthritis progression in mice following intra-articular administration of simvastatin-conjugated gelatin hydrogel.

Abstract

Simvastatin is clinically used for the treatment of hypercholesterolaemia. This study investigated the effects of the intra-articular administration of a simvastatin-conjugated gelatin hydrogel on osteoarthritis (OA) progression in a murine model. The medial meniscus of the knee joint was de-stabilized to induce OA in 10-week-old mice. Mice were then intra-articularly injected with dimethyl sulfoxide (control), drug-free gelatin hydrogel, simvastatin, or simvastatin-conjugated gelatin hydrogel. At 8weeks postsurgery, OA progression was significantly attenuated in the simvastatin-conjugated gelatin hydrogel-treated mice compared with the other three groups. Attenuation of OA in mice treated with simvastatin-conjugated gelatin hydrogel was associated with decreased expression of cartilage-degrading enzymes and interleukin (IL)-1β and increased expression of type II collagen and an autophagic marker, LC3, in the articular cartilage. The effects of simvastatin on gene expression and autophagy in the mouse primary chondrocytes were also examined in the presence or absence of IL-1β. Treatment with simvastatin down-regulated Mmp-13 and Il-1β and up-regulated Col2a1 and autophagic activity. Our findings suggest that the intra-articular administration of simvastatin-conjugated gelatin hydrogel could be used as a new potential therapy for OA.