Nanke Yuki
   Department   School of Nursing, School of Nursing
   Position   Professor
Article types Original article
Language English
Peer review Peer reviewed
Title Geranylgeranylacetone inhibits formation and function of human osteoclasts and prevents bone loss in tail-suspended rats and ovariectomized rats.
Journal Formal name:Calcified tissue international
Abbreviation:Calcif Tissue Int
ISSN code:(0171-967X)0171-967X(Linking)
Domestic / ForeginForegin
Volume, Issue, Page 77(6),pp.376-385
Author and coauthor Nanke Y, Kotake S, Ninomiya T, Furuya T, Ozawa H, Kamatani N
Publication date 2005/12
Summary Vitamin K is used for protecting against osteoporosis. Recently, it has been reported that the inhibitory effect of vitamin K(2) (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-kappaB 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.
DOI 10.1007/s00223-005-0123-7
PMID 16362462