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

摘要

Vitamin K is a fat-soluble vitamin, which is involved in blood coagulation mediated by maintaining the activity of coagulation factors in the liver. VitaminK also has extrahepatic actions and has been shown to prevent bone fractures in clinical studies. In addition, epidemiological studies suggest that a lack of vitaminK is associated with several geriatric diseases, including osteoporosis, osteoarthritis, dementia and arteriosclerosis. It has also been shown that vitaminK contributes to the prevention and treatment of some kinds of malignancies. Recently, we discovered a novel role for vitaminK 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, vitaminK 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 vitaminK are partially mediated by SXR/PXR-dependent signaling. The discoveries of a novel mode of vitaminK action have opened up new possibilities that vitaminK might be useful for prevention or treatment of a variety of diseases that affect the geriatric population.