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

J Bone Miner Res. 1993 May;8(5):535-42. doi: 10.1002/jbmr.5650080504.

Abstract

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.

MeSH terms

  • Animals
  • Bone Resorption / prevention & control*
  • Bone and Bones / drug effects*
  • Bone and Bones / metabolism
  • Calcitriol / pharmacology
  • Calcium / metabolism
  • Dinoprostone / biosynthesis*
  • Dinoprostone / metabolism
  • Hydroxyproline / metabolism
  • Indomethacin / pharmacology
  • Interleukin-1 / pharmacology
  • Mice
  • Mice, Inbred ICR
  • Organ Culture Techniques
  • Parathyroid Hormone / pharmacology
  • Vitamin K / analogs & derivatives*
  • Vitamin K / pharmacology
  • Vitamin K 2 / analogs & derivatives

Substances

  • Interleukin-1
  • Parathyroid Hormone
  • Vitamin K 2
  • Vitamin K
  • menatetrenone
  • Calcitriol
  • Dinoprostone
  • Hydroxyproline
  • Calcium
  • Indomethacin