Vitamin K and rheumatoid arthritis

IUBMB Life. 2008 Jun;60(6):355-61. doi: 10.1002/iub.41.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antirheumatic Agents / pharmacology
  • Apoptosis*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Dose-Response Relationship, Drug
  • Female
  • Fibroblasts / metabolism
  • Humans
  • Models, Biological
  • Rats
  • Reactive Oxygen Species
  • Tetrazolium Salts / pharmacology
  • Thiazoles / pharmacology
  • Vitamin K / metabolism*
  • Vitamin K / therapeutic use*


  • Antirheumatic Agents
  • Reactive Oxygen Species
  • Tetrazolium Salts
  • Thiazoles
  • Vitamin K
  • thiazolyl blue