Inhibitory Effects of Hydrolysable Tannins on Osteoclast Differentiation and Function through Inhibition of Map Kinases and Ap-1/kf-kb Activations

Introduction Recently it has been shown that flavonoids of polyphenolic compounds such as genistein and daidzein isolated from soyfood exert a therapeutic effect on osteoporosis and that they inhibit osteoclast differentiation [1,2]. Moreover, some flavonoids such as quercetin, kaempferol, and condensed tannins such as (-)-epigallocatechin-gallate (EGCG) derived from vegetables, wine, and green tea induce apoptosis of mature osteoclasts in the same dose-range effective for inhibiting bone resorption [3]. Quercetin also has been shown to inhibit osteoclast differentiation of progenitors at low doses [4], and its glycoside, rutin (quercetin-3-O-β-D-rutinoside), has been shown to inhibit ovariectomyinduced osteopenia in rats. However, it was not clear whether hydrolysable tannins also exert similar inhibitory effects on osteoclast differentiation and function. Previously we have shown that furosin, a hydrolysable tannin, also have a potential to inhibit osteoclast differentiation and function by a mechanism involving inhibition of RANKL-induced MAP kinase activation and actin ring formation [5]. Therefore, we asked whether other members of hydrolysable tannins have similar inhibitory effects on osteoclast differentiation and function. In the present study, we investigated the effects of two hydrolysable tannins, named as K10 and K43, on osteoclast differentiation and function, and their influence on RANKL-induced early intracellular signaling pathways.