title: Zinc modifies the effect of phyto-oestrogens on osteoblast and osteoclast differentiation in vitro.
abstract: Osteoblast and osteoclast activity is disrupted in post-menopausal osteoporosis. Thus, to fully address this imbalance, therapies should reduce bone resorption and promote bone formation. Dietary factors such as phyto-oestrogens and Zn have beneficial effects on osteoblast and osteoclast activity. However, the effect of combinations of these factors has not been widely studied. We therefore examined the effect of coumestrol, daidzein and genistein in the presence or absence of zinc sulphate (Zn) on osteoclast and osteoblast activity. Osteoclast differentiation and bone resorption were significantly reduced by coumestrol (10- 7 m), daidzein (10- 5 m) and genistein (10- 7 m); and this direct anti-osteoclastic action was unaffected by Zn (10- 5 m). In addition, Zn augmented the inhibitory effect of phyto-oestrogens on the osteoblast-derived stimulus for osteoclast formation, significantly reducing the ratio of receptor activator of NF-κB ligand (RANKL)-to-osteoprotegerin mRNA expression in human osteoblast. We then examined the effect of these compounds on osteoblast activity. Mineralisation was enhanced by coumestrol (10- 5 to 10- 7 m), daidzein (10- 5 to 10- 6 m) and genistein (10- 5 m); and Zn significantly augmented this response. Zn and phyto-oestrogens also significantly enhanced alkaline phosphatase activity and Runt-related transcription factor 2 (Runx2) mRNA expression. On the other hand, Zn blunted phyto-oestrogen-induced type I collagen and osteocalcin expression and suppressed coumestrol and daidzein-stimulated osterix expression. Zn may therefore modify the anabolic action of phyto-oestrogens, promoting characteristics associated with early rather than late stages of osteoblast differentiation. Our data suggest that while Zn enhances the anti-osteoclastic effect of phyto-oestrogens, it may limit aspects of their anabolic action on bone matrix formation.
authors.affiliation: School of Biomedical and Biological Sciences, Room 404 Davy Building, Drake Circus, Plymouth University, Plymouth              PL4 8AA, UK.
authors.forename: Sahar
authors.initials: S
authors.lastname: Karieb
authors.forename: Simon W
authors.initials: SW
authors.lastname: Fox
mesh_terms: D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001862:Bone Resorption; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D003375:Coumestrol / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology; D008024:Ligands; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053244:Osteoprotegerin; D048789:Phytoestrogens / Q000494:pharmacology*; D000076182:Sp7 Transcription Factor; D000071681:Tartrate-Resistant Acid Phosphatase; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*
chemical_list: D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D007527:Isoenzymes; D007529:Isoflavones; D008024:Ligands; D016328:NF-kappa B; D053244:Osteoprotegerin; D048789:Phytoestrogens; C493709:RUNX2 protein, human; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; C004742:daidzein; D019833:Genistein; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D015032:Zinc; D003375:Coumestrol