THE INHIBITORY EFFECT OF VITAMIN-K-2 (MENATETRENONE) ON BONE-RESORPTION MAY BE RELATED TO ITS SIDE-CHAIN

Although the effects of vitamin K-2 and vitamin K-1 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 K-2 homologues, and vitamin K-1 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)(2)D-3 or 10(-7) M of prostaglandin E(2), and it also inhibited osteoclastlike multinucleated cell (MNC) formation induced by 10(-8) M of 1,25(OH)(2)D-3 in co-culture of spleen cells and stromal cells at the same concentrations, In contrast, the same doses of vitamin K-1 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 K-1, 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.