Hiruma Yuko, Nakahama Ken-ichi, Fujita Hiroshi, Morita Ikuo
Department of Cellular Physiological Chemistry, Graduated School, Tokyo Medical and Dental University 1-5-45, Yushima, Bunkyo-ku, Tokyo, Japan.
Biochem Biophys Res Commun. 2004 Jan 30;314(1):24-30. doi: 10.1016/j.bbrc.2003.12.051.
We comparatively examined the mechanism by which vitamin K(2) (Menatetrenone, MK4) and its side chain component, geranylgeraniol (GGO), inhibited osteoclast formation in the co-culture system of stromal cells with spleen cells. Both MK4 and GGO inhibited osteoclast formation induced by 1alpha,25-dihydroxyvitamin D3 (1,25(OH)(2)D(3)). MK4, but not GGO, inhibited cyclooxygenase-2 (COX-2) expression and prostaglandin E(2) (PGE(2)) production in the co-culture system. To elucidate the precise mechanism of the inhibitory effect of GGO on osteoclast formation, the co-cultured cells were stimulated with PGE(2). GGO, but not MK4, inhibited osteoclast formation via suppression of the receptor activator of NF-kappaB ligand (RANKL) expression. Moreover, GGO abolished the disruption of osteoclastic actin rings induced by nitrogen-containing bisphosphonate (N-BP), whereas MK4 did not affect it at all. These data suggest that MK4 inhibited osteoclast formation independently of GGO, and that MK4, but not GGO, has no competitive action on the anti-osteoporotic effect of N-BP.
我们比较研究了维生素K(2)（甲萘醌四烯甲萘醌，MK4）及其侧链成分香叶基香叶醇（GGO）在基质细胞与脾细胞共培养体系中抑制破骨细胞形成的机制。MK4和GGO均抑制1α,25 - 二羟基维生素D3（1,25(OH)(2)D(3)）诱导的破骨细胞形成。在共培养体系中，MK4而非GGO抑制环氧合酶 - 2（COX - 2）表达和前列腺素E(2)（PGE(2)）产生。为阐明GGO对破骨细胞形成抑制作用的精确机制，用PGE(2)刺激共培养细胞。GGO而非MK4通过抑制核因子κB受体活化因子配体（RANKL）表达抑制破骨细胞形成。此外，GGO消除了含氮双膦酸盐（N - BP）诱导的破骨细胞肌动蛋白环的破坏，而MK4对此毫无影响。这些数据表明，MK4独立于GGO抑制破骨细胞形成，且MK4而非GGO对N - BP的抗骨质疏松作用无竞争作用。
