Vitamin K and rheumatoid arthritis.
Vitamin K2 [menaquinone-4 (MK-4)] has been reported to induce apoptosis in hepatocellular carcinoma, leukemia, and MDS cell lines. The effects of MK-4 on the development of arthritis have never been addressed so far. In this study, we investigated the effect of MK-4 upon the proliferation of rheumatoid synovial cells and the development of arthritis in collagen-induced arthritis (CIA). We analyzed the effect of MK-4 on the proliferation of fibroblast-like synoviocytes (FLSs) using the 3-(4,5-demethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The proapoptotic effect of MK-4 upon FLS 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 CIA in female dark agouti rats. Our results indicated that MK-4 inhibited the proliferation of FLS and the development of CIA in a dose-dependent manner. We concluded that MK-4 may represent a new agent for the treatment of RA in the setting of combination therapy with other disease-modifying antirheumatic drugs.
Okamoto
Hiroshi
H
Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan. hokamoto@ior.twmu.ac.jp
D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology; D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D051381:Rats; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014812:Vitamin K / Q000378:metabolism* / Q000627:therapeutic use*
D018501:Antirheumatic Agents; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D014812:Vitamin K; C022616:thiazolyl blue