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Vitamin K: Novel molecular mechanisms of action and its roles in osteoporosis
Author(s) -
Azuma Kotaro,
Ouchi Yasuyoshi,
Inoue Satoshi
Publication year - 2014
Publication title -
geriatrics and gerontology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.823
H-Index - 57
eISSN - 1447-0594
pISSN - 1444-1586
DOI - 10.1111/ggi.12060
Subject(s) - pregnane x receptor , medicine , osteoporosis , vitamin d and neurology , endocrinology , vitamin , vitamin k2 , calcitriol receptor , nuclear receptor , pharmacology , biology , biochemistry , gene , transcription factor
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. Geriatr Gerontol Int 2014; 14: 1–7.