Vitamin K-dependent bone proteins

Author: Matilde Demarchi
Date: 21/02/2012


Over the past 20 years, several additional proteins that are unrelated to coagulation were identified as requiring this same vitamin K–dependent posttranslational modification. These VKD proteins seem to have a variety of physiologic roles in bone metabolism, vascular repair, preventing vascular calcification, cell-cell adhesion, cell cycle regulation, and signal transduction.Relative to bone, there are 3 known VKD proteins: OC, matrix Gla protein, and protein S. Matrix Gla protein and protein S are also synthesized by a wide range of tissues, including chondrocytes, vascular smooth muscle cells, and epithelial cells. the vitamin K-dependent matrix Gla-protein is also involved in vascular calcification . Although on a molecular level its mechanism of action is not completely understood, it is generally accepted that MGP is a potent inhibitor of arterial calcification.
Furthermore, vitamin K2 also inhibits the expression of the osteoclast differentiation factor (ODF)/RANK ligand, tartrate-resistant acid phosphatase activity, and mononuclear cell formation, and induces osteoclast apoptosis in vitro.
Osteoclast formation requires the presence of RANK ligand (receptor activator of nuclear factor κβ) and M-CSF (Macrophage colony-stimulating factor). These membrane bound proteins are produced by neighbouring stromal cells and osteoblasts, thus requiring direct contact between these cells and osteoclast precursors.

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