Dried plum polyphenols attenuate the detrimental effects of TNF-α on osteoblast function coincident with up-regulation of Runx2, Osterix and IGF-I

Previous studies have demonstrated that dried plums which contain high amounts of polyphenols can restore boric mass and structure, and significantly increase indices of boric formation. The purpose of this Study wits to determine how dried plum polyphenols influence osteoblast activity and mineralized nodule formation under normal and inflammatory conditions. MC3T3-E1 cells were plated and pretreated with dried plum polyphenols (0, 2.51 5 10 and 20 mu g/ml) and 24 It later Stimulated with TNF-alpha (0 or 1.0 ng/ml). The 5, 10 and 20 mu g/ml doses of polyphenols significantly increased intracellular ALP activity under normal conditions at 7 and 14 days, and restored the TNF-alpha-induced suppression of intracelluar ALP activity by 14 days (P<.001). Polyphenols also increased mineralized nodule formation under normal and inflammatory conditions. In the absence of TNF-alpha, 5 mu g/ml of polyphenols significantly up-regulated the growth factor, IGF-I, compared to controls, and the 5 and 10 mu g/ml doses increased the expression of lysyl oxidase; involved in collagen crosslinking. TNF-alpha decreased the expression of Runx2, Osterix and IGF-I. and polyphenols restored their mRNA levels to that of the controls. Although TNF-alpha failed to alter lysyl oxidase at IS h. the polyphenols up-regulated its expression (P<.05) in the presence of TNF-alpha. As expected, TNF-alpha up-regulated RANKL mRNA and polyphenols Suppressed RANKI. expression without altering OPG. Based on these findings, we conclude that dried plum polyphenols enhance osteoblast activity and function by up-regulating Runx2, Osterix and IGF-I and increasing lysyl oxidase expression, and at the same time attenuate osteoclastogenesis signaling. (C) 2009 Elsevier Inc. All rights reserved.