title: Vitamin K: novel molecular mechanisms of action and its roles in osteoporosis.
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.
authors.affiliation: Department of Geriatric Medicine, The University of Tokyo, Tokyo, Japan; Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Azuma
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Ouchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D006801:Humans; D010024:Osteoporosis / Q000097:blood / Q000188:drug therapy*; D014812:Vitamin K / Q000627:therapeutic use*; D014815:Vitamins / Q000627:therapeutic use
chemical_list: D014815:Vitamins; D014812:Vitamin K
keywords: pregnane X receptor; steroid and xenobiotic receptor; vitamin K; γ-glutamyl carboxylase