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Anti‐arthritis effects of vitamin K2 (menaquinone‐4) − a new potential therapeutic strategy for rheumatoid arthritis

Vitamin K2 (menaquinone‐4, MK‐4) has been reported to induce apoptosis in hepatocellular carcinoma, leukemia and myelodysplastic syndrome cell lines. The effects of MK‐4 on the development of arthritis have never been addressed thus far. In the present study, we investigated the effect of MK‐4 upon the proliferation of rheumatoid synovial cells and the development of arthritis in collagen‐induced arthritis. We analyzed the effect of MK‐4 on the proliferation of fibroblast‐like synoviocytes using the 3‐(4,5‐demethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. The pro‐apoptotic effect of MK‐4 upon fibroblast‐like synoviocytes was investigated with annexin V staining and DNA fragmentation and caspase 3/7 assays. Moreover, we analyzed the effect of MK‐4 on the development of collagen‐induced arthritis in female dark agouti rats. Our results indicated that MK‐4 inhibited the proliferation of fibroblast‐like synoviocytes and the development of collagen‐induced arthritis in a dose‐dependent manner. We conclude that MK‐4 may represent a new agent for the treatment of rheumatoid arthritis in the setting of combination therapy with other disease‐modifying antirheumatic drugs.