Vitamin K2 (menatetrenone) inhibits prostaglandin synthesis in cultured human osteoblast-like periosteal cells by inhibiting prostaglandin H synthase activity.
Prostaglandin (PG) E2, a potent bone-resorbing agent, is synthesized in osteoblast-like cells. Since vitamin K reportedly plays an important role in bone metabolism, we investigated the effects of vitamin K2 (menatetrenone) on PGE2 production by human osteoblast-like periosteal cells. In cells incubated with menatetrenone (1 microgram/mL = 2.25 x 10(-6) M) for 2 days, PGE2 production was reduced to 50% of that in untreated control cells. This inhibition was dose and time dependent for up to 10 micrograms/mL and 20 days, respectively, and involved two major steps. In one of these menatetrenone at doses of 0.5-10 micrograms/mL dose dependently inhibited the calcium ionophore A23187-induced release of arachidonic acid (AA) from membrane phospholipids, and in the other the conversion of AA to PG was inhibited, as evidenced by the PG-synthesizing activity in the homogenates of menatetrenone-treated cells with AA being lower than that in untreated cells. The inhibitory effect was almost identical to that for PG production. The PG synthesizing activity in cell homogenates was inhibited only by a high concentration of menatetrenone (10 micrograms/mL) when this was added directly. Menatetrenone (1 microgram/mL) also inhibited 52% of the purified PGH synthase activity from a ram seminal vesicle. This study shows that menatetrenone inhibited PGE2 release from cells by inhibiting both PG production steps, AA release from the membrane and PG synthesizing activity with AA. Inhibition of PGE2 production by menatetrenone might be important in improving bone metabolism.
Koshihara
Y
Y
Department of Biosignal Research, Tokyo Metropolitan Institute of Gerontology, Japan.
Hoshi
K
K
Shiraki
M
M
D000328:Adult; D016718:Arachidonic Acid / Q000378:metabolism; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010521:Periosteum / Q000166:cytology; D010740:Phospholipases / Q000037:antagonists & inhibitors; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D014812:Vitamin K / Q000031:analogs & derivatives* / Q000494:pharmacology; D024482:Vitamin K 2 / Q000031:analogs & derivatives
D016861:Cyclooxygenase Inhibitors; D024482:Vitamin K 2; D014812:Vitamin K; C030814:menatetrenone; D016718:Arachidonic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D010740:Phospholipases; D015232:Dinoprostone