Calcified Tissue International

, Volume 77, Issue 6, pp 376–385

Geranylgeranylacetone Inhibits Formation and Function of Human Osteoclasts and Prevents Bone Loss in Tail-Suspended Rats and Ovariectomized Rats

  • Y. Nanke
  • S. Kotake
  • T. Ninomiya
  • T. Furuya
  • H. Ozawa
  • N. Kamatani
Article

DOI: 10.1007/s00223-005-0123-7

Cite this article as:
Nanke, Y., Kotake, S., Ninomiya, T. et al. Calcif Tissue Int (2005) 77: 376. doi:10.1007/s00223-005-0123-7

Abstract

Vitamin K is used for protecting against osteoporosis. Recently, it has been reported that the inhibitory effect of vitamin K2 (menatetrenone) on bone resorption may be related to its side chain. Geranylgeranylacetone (GGA), known as teprenone, an antiulcer drug, has almost the same chemical structure as that of the side chain of menatetrenone. We hypothesized that GGA also has an inhibitory effect on osteoclastogenesis both in vitro and in vivo. GGA in pharmacological concentrations directly inhibited osteoclastogenesis from human monocytes induced by soluble receptor activator of nuclear factor-κB ligand. In addition, GGA induced degradation of actin rings in mature osteoclasts, which was reversed by adding geranylgeranylpyrophosphatase. Moreover, GGA increased the bone mineral density of total femur, proximal metaphysis, and diaphysis of femur in ovariectomized rats. GGA also prevented bone loss induced by hindlimb unloading in tail-suspended rats. These results indicate that GGA prevents bone loss by maintaining a positive balance of bone turnover through suppression of both the formation and the activity of osteoclasts. Thus, GGA could be used to prevent and improve osteoporosis.

Keywords

OsteoclastBone mineral densityOsteoporosisSpace flightBisphosphonate

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Y. Nanke
    • 1
  • S. Kotake
    • 1
  • T. Ninomiya
    • 2
  • T. Furuya
    • 1
  • H. Ozawa
    • 2
  • N. Kamatani
    • 1
  1. 1.Institute of RheumatologyTokyo Women’s Medical UniversityShinjuku-kuJapan
  2. 2.Division of Hard Tissue Research, Institute for Oral ScienceMastumoto Dental UniversityShiojiriJapan