Takeuchi Y, Suzawa M, Fukumoto S, Fujita T
Division of Endocrinology, Department of Medicine, University of Tokyo School of Medicine, Tokyo, Japan.
Bone. 2000 Dec;27(6):769-76. doi: 10.1016/s8756-3282(00)00396-3.
Several lines of evidence suggest that vitamin K has nutritional and pharmacological effects against bone loss. To clarify effects of vitamin K on bone marrow cells, which contains progenitors of both osteoblasts and osteoclasts, we examined mouse bone marrow cell cultures in the presence of vitamin K(1) (K1) and menatetrenone (MK4), a vitamin K(2) with four isoprene units. Treatment with MK4 but not K1 inhibited the formation of adipocytes and stimulated alkaline phosphatase activity, an early differentiation marker of osteoblast. Although nuclear receptor PPARgamma2 plays a pivotal role in adipogenesis, MK4 had no effects on the expression of PPARgamma2 mRNA and PPARgamma2-dependent transcriptional activity. MK4 inhibited the expression of osteoclast differentiation factor (ODF)/RANK ligand and the formation of osteoclast-like cells induced by 1,25-dihydroxyvitamin D(3). These results suggest that MK4 specifically influences differentiation and functions of bone marrow cells to inhibit adipogenesis and osteoclastogenesis. At the expense of adipogenesis, MK4 might stimulate osteoblastogenesis in bone marrow cells. Therefore, MK4 may favor bone metabolism to spare bone mass as a compound that modulates cellular differentiation and functions in bone marrow in addition to as a nutrient factor.
多项证据表明，维生素K对骨质流失具有营养和药理作用。为了阐明维生素K对骨髓细胞的影响，骨髓细胞包含成骨细胞和破骨细胞的祖细胞，我们在维生素K1（K1）和甲萘醌（MK4，一种具有四个异戊二烯单元的维生素K2）存在的情况下检测了小鼠骨髓细胞培养物。用MK4而非K1处理可抑制脂肪细胞的形成并刺激碱性磷酸酶活性，碱性磷酸酶是成骨细胞早期分化的标志物。尽管核受体PPARγ2在脂肪生成中起关键作用，但MK4对PPARγ2 mRNA的表达和PPARγ2依赖性转录活性没有影响。MK4抑制破骨细胞分化因子（ODF）/RANK配体的表达以及由1,25-二羟基维生素D3诱导的破骨样细胞的形成。这些结果表明，MK4特异性影响骨髓细胞的分化和功能，以抑制脂肪生成和破骨细胞生成。以脂肪生成为代价，MK4可能会刺激骨髓细胞中的成骨细胞生成。因此，MK4可能有利于骨代谢以保留骨量，作为一种除了作为营养因子外还能调节骨髓细胞分化和功能的化合物。
