Abstract
Vitamin K is widely 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 (sRANKL). In addition, GGA induced degradation of actin rings in mature osteoclasts, which was rescued by adding geranylgeranylpyrophosphatase. These results indicate that GGA increases bone mass 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.
