Menatetrenone inhibits bone resorption partly through inhibition of PGE2 synthesis in vitro

Abstract

We studied the effect of menatetrenone, a vitamin K₂ homolog, on bone resorption stimulated by interleukin‐1α (IL‐1α), 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‐1α (0.1–100 U/ml), 1,25‐(OH)₂D₃ (10¹⁰‐10⁻⁷ M), PGE₂ (10⁻⁹‐10⁻⁶ M), and PTH (3 × 10⁻⁸‐3 × 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‐1α and partially inhibited bone resorption induced by 1,25‐(OH)₂D₃. However, indomethacin did not affect the action of PGE₂ or PTH. Menatetrenone (3 × 10⁻⁶‐3 × 10⁻⁵ M) inhibited the bone resorption induced by IL‐1α (2 U/ml), PGE₂ (10⁻⁷ M), PTH (3 × 10⁻⁷ M), and 1,25‐(OH)₂D₃ (3 × 10⁻¹⁰ M) in a dose‐dependent manner. Menatetrenone also inhibited the PGE₂ production stimulated by IL‐1α. These results indicate that menatetrenone may inhibit bone resorption through at least two different mechanisms; one possibly is an inhibitory effect on prostaglandin production.