title: Effect of vitamin K in bone metabolism and vascular calcification: A review of mechanisms of action and evidences.
abstract: Osteoporosis is a public health concern associated with an increased risk of bone fractures and vascular calcification. Vitamin K presents unique benefits on these issues, although understudied. The two main forms of vitamin K are phylloquinone (vitamin K1) and menaquinone (vitamin K2). In this study, it was especially investigated the action of vitamin K2in bones and vessels. Vitamin K2has shown to stimulate bone formation by promoting osteoblast differentiation and carboxylation of osteocalcin, and increasing alkaline phosphatase, insulin-like growth factor-1, growth differentiation factor-15, and stanniocalcin 2 levels. Furthermore, vitamin K2reduces the pro-apoptotic proteins Fas and Bax in osteoblasts, and decreases osteoclast differentiation by increasing osteoprotegerin and reducing the receptor activator of nuclear factor kappa-B ligand. In blood vessels, vitamin K2reduces the formation of hydroxyapatite, through the carboxylation of matrix Gla protein and Gla rich protein, inhibits the apoptosis of vascular smooth muscle cells, by increasing growth arrest-specific gene 6, and reduces the transdifferentiation of vascular smooth muscle cells to osteoblasts. The commonly used dosage of vitamin K2in human studies is 45 mg/day and its application can be an interesting strategy in benefitting bone and vascular health, especially to osteoporotic post-menopausal women.
authors.affiliation: a Departamento de Bioquímica e Biologia Molecular , Universidade Federal de Viçosa , Minas Gerais , Brazil.
authors.forename: Julia Khéde Dourado
authors.initials: JKD
authors.lastname: Villa
authors.affiliation: a Departamento de Bioquímica e Biologia Molecular , Universidade Federal de Viçosa , Minas Gerais , Brazil.
authors.forename: Marisa Alves Nogueira
authors.identifier: http://orcid.org/0000-0002-3370-4149
authors.initials: MAN
authors.lastname: Diaz
authors.affiliation: a Departamento de Bioquímica e Biologia Molecular , Universidade Federal de Viçosa , Minas Gerais , Brazil.
authors.forename: Virgínia Ramos
authors.identifier: http://orcid.org/0000-0001-8611-4663
authors.initials: VR
authors.lastname: Pizziolo
authors.affiliation: b Departamento de Nutrição e Saúde , Universidade Federal de Viçosa , Minas Gerais , Brazil.
authors.forename: Hércia Stampini Duarte
authors.initials: HSD
authors.lastname: Martino
mesh_terms: D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism*; D054338:Cell Transdifferentiation; D006801:Humans; D015675:Osteocalcin / Q000378:metabolism; D010024:Osteoporosis / Q000188:drug therapy / Q000517:prevention & control; D061205:Vascular Calcification / Q000517:prevention & control*; D014812:Vitamin K / Q000502:physiology* / Q000627:therapeutic use*; D024482:Vitamin K 2
chemical_list: D015675:Osteocalcin; D024482:Vitamin K 2; D014812:Vitamin K
keywords: Menaquinone; cardiovascular disease; osteoporosis; postmenopause