| First Author | Azuma K | Year | 2015 |
| Journal | J Bone Miner Res | Volume | 30 |
| Issue | 7 | Pages | 1245-54 |
| PubMed ID | 25600070 | Mgi Jnum | J:315360 |
| Mgi Id | MGI:6830227 | Doi | 10.1002/jbmr.2463 |
| Citation | Azuma K, et al. (2015) Osteoblast-Specific gamma-Glutamyl Carboxylase-Deficient Mice Display Enhanced Bone Formation With Aberrant Mineralization. J Bone Miner Res 30(7):1245-54 |
| abstractText | Vitamin K is a fat-soluble vitamin that is necessary for blood coagulation. In addition, it has bone-protective effects. Vitamin K functions as a cofactor of gamma-glutamyl carboxylase (GGCX), which activates its substrates by carboxylation. These substrates are found throughout the body and examples include hepatic blood coagulation factors. Furthermore, vitamin K functions as a ligand of the nuclear receptor known as steroid and xenobiotic receptor (SXR) and its murine ortholog, pregnane X receptor (PXR). We have previously reported on the bone-protective role of SXR/PXR signaling by demonstrating that systemic Pxr-knockout mice displayed osteopenia. Because systemic Ggcx-knockout mice die shortly after birth from severe hemorrhage, the GGCX-mediated effect of vitamin K on bone metabolism has been difficult to evaluate. In this work, we utilized Ggcx-floxed mice to generate osteoblast-specific GGCX-deficient (Ggcx(Deltaobl/Deltaobl)) mice by crossing them with Col1-Cre mice. The bone mineral density (BMD) of Ggcx(Deltaobl/Deltaobl) mice was significantly higher than that of control Col1-Cre (Ggcx(+/+)) mice. Histomorphometrical analysis of trabecular bones in the proximal tibia showed increased osteoid volume and a higher rate of bone formation in Ggcx(Deltaobl/Deltaobl) mice. Histomorphometrical analysis of cortical bones revealed a thicker cortical width and a higher rate of bone formation in Ggcx(Deltaobl/Deltaobl) mice. Electron microscopic examination revealed disassembly of mineralized nodules and aberrant calcification of collagen fibers in Ggcx(Deltaobl/Deltaobl) mice. The mechanical properties of bones from Ggcx(Deltaobl/Deltaobl) mice tended to be stronger than those from control Ggcx(+/+) mice. These results suggest that GGCX in osteoblasts functions to prevent abnormal mineralization in bone formation, although this function may not be a prerequisite for the bone-protective effect of vitamin K. |
