tailieunhanh - Báo cáo khoa học: 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. | ễFEBS Journal Anti-arthritis effects of vitamin K2 menaquinone-4 - a new potential therapeutic strategy for rheumatoid arthritis Hiroshi Okamoto Kumi Shidara Daisuke Hoshi and Naoyuki Kamatani Institute of Rheumatology Tokyo Women s MedicalUniversity Japan Keywords apoptosis collagen type II-induced arthritis rheumatoid arthritis vitamin K2 menaquinone-4 Correspondence H. Okamoto Institute of Rheumatology Tokyo Women s MedicalUniversity 10-22 Kawada-cho Shinjuku Tokyo 162-0054 Japan Fax 81 3 5269 1726 Tel 81 3 5269 1725 E-mail hokamoto@ Received 9 December 2006 revised 26 June 2007 accepted 12 July 2007 doi 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-de-methylthiazol-2-yl -2 5-diphenyltetrazolium bromide assay. The pro-apop-totic 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 diseasemodifying antirheumatic drugs. Vitamin K is a generic term for compounds that include phytonadione vitamin K1 the menaquinone series vitamin K2 and menadione vitamin K3 . These .