Vitamin K: novel molecular mechanisms of action and its roles in osteoporosis

Geriatr Gerontol Int. 2014 Jan;14(1):1-7. doi: 10.1111/ggi.12060. Epub 2013 Mar 26.

Abstract

Vitamin K is a fat-soluble vitamin, which is involved in blood coagulation mediated by maintaining the activity of coagulation factors in the liver. Vitamin K also has extrahepatic actions and has been shown to prevent bone fractures in clinical studies. In addition, epidemiological studies suggest that a lack of vitamin K is associated with several geriatric diseases, including osteoporosis, osteoarthritis, dementia and arteriosclerosis. It has also been shown that vitamin K contributes to the prevention and treatment of some kinds of malignancies. Recently, we discovered a novel role for vitamin K as a ligand of the nuclear receptor, steroid and xenobiotic receptor (SXR), and its murine ortholog, pregnane X receptor (PXR). In addition to its established roles as a cofactor of γ-glutamyl carboxylase (GGCX) in mediating post-transcriptional modifications, vitamin K has a different mode of action mediated by transcriptional regulation of SXR/PXR target genes. Analysis of bone tissue from PXR-deficient mice showed that the bone protective effects of vitamin K are partially mediated by SXR/PXR-dependent signaling. The discoveries of a novel mode of vitamin K action have opened up new possibilities that vitamin K might be useful for prevention or treatment of a variety of diseases that affect the geriatric population.

Keywords: pregnane X receptor; steroid and xenobiotic receptor; vitamin K; γ-glutamyl carboxylase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood Coagulation / drug effects*
  • Humans
  • Osteoporosis / blood
  • Osteoporosis / drug therapy*
  • Vitamin K / therapeutic use*
  • Vitamins / therapeutic use

Substances

  • Vitamins
  • Vitamin K