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SAT0161 Menatetrenone acts directly on circulating human osteoclast precursors
  1. T Hirayama,
  2. H Taira,
  3. O Kudo,
  4. I Itonaga,
  5. T Torisu,
  6. Y Fujikawa
  1. Department of Orthopaedic Surgery, Oita Medical University, Oita-Gun, Japan

Abstract

Background Vitamin K is known to be an essential cofactor in the post-translational gamma-carboxylation of clotting factors. Since the gamma-carboxyglutamic acid-containing protein, osteocalcin, was discovered in bone matrix, vitamin K was thought to play a role in bone metabolism. Both in vitro and in vivo studies have shown that menatetrenone, a vitamin K2 homologue, can act directly on bone metabolism.

Objectives Although the relationship between menatetrenone and bone resorption appears clear,1,2 it is still not certain whether menatetrenone act directly on osteoclast precursors to influence their differentiation into osteoclasts. In this study, we have invetgated whether menatetrenone has a direct effect on circulating osteoclast precursors to influence osteoclast differentiation.

Methods Monocytes were cultured with osteoprotegerin ligand (OPGL) in the presence of macrophage stimulating factor (M-CSF) on glass coverslips and dentine slices. Menatetrenone or vitamin K1 was then added to the cultures in 10–7, -6, -5 (M) respectively. Geranylgeraniol or phytol (alcohol forms of the respective side chain of menatetrenone and vitamin K1) was also added to the cultures. After 7 and 14 days incubation, cultures were assessed for cytochemical and functional evidence of osteoclast differentiation.

Results The number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs) and the area of lacunar resorption were decreased when menatetrenone was added. Dose-dependent inhibition of osteoclast formation and lacunar resorption was seen. Vitamin K1, however, did not inhibite the formation of TRAP positive MNCs nor lacunar resorption. The addition of geranylgeraniol in the cultures inhibited osteoclast formation in a dose dependent manner. Phytol did not affect the number of TRAP-positive MNCs nor lacunar resorption.

Conclusion Menatetrenone not only influence osteoclast formation in the presence of bone stromal cells but also act directly on circulating osteoclast precursors to influence osteoclast differentiation. The inhibitory effect of menatetrenone on osteoclast formation is not due to gamma-carboxylation and the side chain of menatetrenone may play an important role in this inhibitory effect.

References

  1. Akiyama Y, Hara K, Tajima T, Murota S, Morita I. Effect of vitaminK2 (menatetrenone) on osteoclast-like cell formation in mouse bone marrow culture. Eur J Pharmacol. 1994;263:181–5

  2. Hara K, Akiyama Y, Ohkawa I, Tajima T. The effect of menatetrenone on prednisolone-induced bone loss in rats. Bone 1993;14: 813–18

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