ビタミンKと骨代謝(<特集>第65回大会シンポジウム「臨床とビタミンUp-Date」)

抄録

Vitamin K (VK) is a fat-soluble vitamin that is essential for blood coagulation as well as bone metabolism. VK consists of 3 forms due to the difference of side chains bound to naphtoquinone ring: VK_1 (phylloquinone), VK_2 (menaquinone) and, VK_3 (menadione). In Japan, VK_2 is clinically used as a therapeutic agent for osteoporosis. VK functions as a co-factor of VK-dependent γ-glutamyl carboxylase (GGCX) in mediating post-translational modifications. As GGCX-dependent γ-carboxylated (Gla) proteins expressed in bone, osteocalcin (OC) and matrix Gla protein (MGP) are known to play modulatory roles in bone metabolism. On the other hand, VK_2 also regulates the transcription of bone-related genes in osteoblasts through activating steroid X receptor (SXR)/pregnane X receptor (PXR), as well as enhancing the phosphorylation of protein kinase A (PKA). Recent studies have revealed that osteoblast-derived OC also exerts a hormone-like action that controls bone metabolism and energy metabolism. Overall, VK is an essential nutrient for bone metabolism through modulating multiple signaling pathways mediated by GGCX, SXR, PKA, and VK-dependent proteins