Hara K, Akiyama Y, Nakamura T, Murota S, Morita I
Pharmacological Evaluation Section, Department of Drug Research II, Eisai Co., Ltd., Tokyo, Japan.
Bone. 1995 Feb;16(2):179-84. doi: 10.1016/8756-3282(94)00027-w.
Although the effects of vitamin K2 and vitamin K1 on bone metabolism have been reported, the difference between them has not been investigated. We now show the effects of menatetrenone, one of the vitamin K2 homologues, and vitamin K1 on bone resorption. Menatetrenone at greater than 3 x 10(-6) M significantly inhibited the calcium release from mouse calvaria induced by 3 x 10(-10) M of 1,25(OH)2D3 or 10(-7) M of prostaglandin E2, and it also inhibited osteoclast-like multinucleated cell (MNC) formation induced by 10(-8) M of 1,25(OH)2D3 in co-culture of spleen cells and stromal cells at the same concentrations. In contrast, the same doses of vitamin K1 had no effects on bone resorption and MNC formation in these in vitro systems. The inhibitory effect of menatetrenone on the calcium release from calvaria was not affected by the addition of 3 x 10(-5) M of warfarin, an inhibitor of vitamin K cycle. The same concentration of geranylgeraniol, the side-chain component of menatetrenone at the 3-position of the naphthoquinone, inhibited tartrate-resistant acid phosphatase (TRACP) activity and MNC formation to the same degree as menatetrenone. Phytol, the side-chain component of vitamin K1, did not affect TRACP activity at all doses tested, but weakly inhibited MNC formation. Moreover, multi-isoprenyl alcohols of two to seven units, except geranylgeraniol which contains four units, did not effect MNC formation. These findings suggest that the inhibitory effect of menatetrenone on bone resorption is not due to gamma-carboxylation and that the side chain of menatetrenone may play an important role in this inhibitory effect.
尽管已有报道维生素K2和维生素K1对骨代谢的影响，但它们之间的差异尚未得到研究。我们现在展示了维生素K2同系物之一甲萘醌和维生素K1对骨吸收的影响。浓度大于3×10⁻⁶ M的甲萘醌显著抑制了由3×10⁻¹⁰ M的1,25(OH)₂D₃或10⁻⁷ M的前列腺素E₂诱导的小鼠颅骨钙释放，并且在相同浓度下，它还抑制了在脾细胞和基质细胞共培养中由10⁻⁸ M的1,25(OH)₂D₃诱导的破骨细胞样多核细胞（MNC）形成。相比之下，相同剂量的维生素K1对这些体外系统中的骨吸收和MNC形成没有影响。甲萘醌对颅骨钙释放的抑制作用不受维生素K循环抑制剂3×10⁻⁵ M华法林添加的影响。萘醌3位上甲萘醌的侧链成分香叶基香叶醇的相同浓度，对抗酒石酸酸性磷酸酶（TRACP）活性和MNC形成的抑制程度与甲萘醌相同。维生素K1的侧链成分叶绿醇在所有测试剂量下均不影响TRACP活性，但对MNC形成有微弱抑制作用。此外，除了含有四个单元的香叶基香叶醇外，两到七个单元的多异戊烯醇对MNC形成没有影响。这些发现表明，甲萘醌对骨吸收的抑制作用不是由于γ-羧化作用，并且甲萘醌的侧链可能在这种抑制作用中起重要作用。
