フルヤ　タケフミ   古谷　武文    所属   医学部 医学科（東京女子医科大学病院）    職種   非常勤講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Geranylgeranylacetone inhibits formation and function of human osteoclasts and prevents bone loss in tail-suspended rats and ovariectomized rats.
掲載誌名	正式名：Calcified tissue international 略　 称：Calcif Tissue Int ISSNコード：(0171-967X)0171-967X(Linking)
掲載区分	国外
巻・号・頁	77(6),pp.376-385
著者・共著者	Nanke Y, Kotake S, Ninomiya T, Furuya T, Ozawa H, Kamatani N
発行年月	2005/12
概要	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