Menatetrenone inhibits bone resorption partly through inhibition of PGE2 synthesis in vitro.
We studied the effect of menatetrenone, a vitamin K2 homolog, on bone resorption stimulated by interleukin-1 alpha (IL-1 alpha), prostaglandin E2 (PGE2), parathyroid hormone (PTH), and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Bone-resorbing activity was assessed by measurement of calcium and hydroxyproline in the media and calvariae. IL-1 alpha (0.1-100 U/ml), 1,25-(OH)2D3 (10(-10)-10(-7) M), PGE2 (10(-9)-10(-6) M), and PTH (3 x 10(-8)-3 x 10(-7) M) dose dependently increased the levels of calcium and hydroxyproline in the medium. Indomethacin (10(-6) M) completely inhibited bone resorption induced by IL-1 alpha and partially inhibited bone resorption induced by 1,25-(OH)2D3. However, indomethacin did not affect the action of PGE2 or PTH. Menatetrenone (3 x 10(-6)-3 x 10(-5) M) inhibited the bone resorption induced by IL-1 alpha (2 U/ml), PGE2 (10(-7) M), PTH (3 x 10(-7) M), and 1,25-(OH)2D3 (3 x 10(-10) M) in a dose-dependent manner. Menatetrenone also inhibited the PGE2 production stimulated by IL-1 alpha. These results indicate that menatetrenone may inhibit bone resorption through at least two different mechanisms; one possibly is an inhibitory effect on prostaglandin production.
Department of Drug Research II, Eisai Co., Ltd., Tokyo, Japan.
K
K
Hara
Y
Y
Akiyama
T
T
Tajima
M
M
Shiraki
D000818:Animals; D001862:Bone Resorption / Q000517:prevention & control*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis* / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009924:Organ Culture Techniques; D010281:Parathyroid Hormone / Q000494:pharmacology; D014812:Vitamin K / Q000031:analogs & derivatives* / Q000494:pharmacology; D024482:Vitamin K 2 / Q000031:analogs & derivatives
D007375:Interleukin-1; D010281:Parathyroid Hormone; D024482:Vitamin K 2; D014812:Vitamin K; C030814:menatetrenone; D002117:Calcitriol; D015232:Dinoprostone; D006909:Hydroxyproline; D002118:Calcium; D007213:Indomethacin