Phytoestrogens directly inhibit TNF-α-induced bone resorption in RAW264.7 cells by suppressing c-fos-induced NFATc1 expression.
dc.contributor.author | Karieb, S | |
dc.contributor.author | Fox, Simon | |
dc.date.accessioned | 2023-02-15T15:28:04Z | |
dc.date.available | 2023-02-15T15:28:04Z | |
dc.date.issued | 2011-02 | |
dc.identifier.issn | 0730-2312 | |
dc.identifier.issn | 1097-4644 | |
dc.identifier.uri | http://hdl.handle.net/10026.1/20388 | |
dc.description.abstract |
TNF-α-induced osteoclastogenesis is central to post-menopausal and inflammatory bone loss, however, the effect of phytoestrogens on TNF-α-induced bone resorption has not been studied. The phytoestrogens genistein, daidzein, and coumestrol directly suppressed TNF-α-induced osteoclastogenesis and bone resorption. TRAP positive osteoclast formation and resorption area were significantly reduced by genistein (10(-7) M), daidzein (10(-5) M), and coumestrol (10(-7) M), which was prevented by the estrogen antagonist ICI 182,780. TRAP expression in mature TNF-α-induced osteoclasts was also significantly reduced by these phytoestrogen concentrations. In addition, in the presence of ICI 182,780 genistein and coumestrol (10(-5) -10(-6) M) augmented TNF-α-induced osteoclast formation and resorption. However, this effect was not observed in the absence of estrogen antagonist indicating that genistein's and coumestrol's ER-dependent anti-osteoclastic action normally negates this pro-osteoclastic effect. To determine the mechanism mediating the anti-osteoclastic action we examined the effect of genistein, coumestrol, and daidzein on caspase 3/7 activity, cell viability and expression of key genes regulating osteoclast differentiation and fusion. While anti-osteoclastic phytoestrogen concentrations had no effect on caspase 3/7 activity or cell viability they did significantly reduce TNF-α-induced c-fos and NFATc1 expression in an ER dependent manner and also inhibited NFATc1 nuclear translocation. Significant decreases in NFκB and DC-STAMP levels were also noted. Interestingly, constitutive c-fos expression prevented the anti-osteoclastic action of phytoestrogens on differentiation, resorption and NFATc1. This suggests that phytoestrogens suppress TNF-α-induced osteoclastogenesis via inhibition of c-fos-dependent NFATc1 expression. Our data provides further evidence that phytoestrogens have a potential role in the treatment of post-menopausal and inflammatory bone loss directly inhibiting TNF-α-induced resorption. | |
dc.format.extent | 476-487 | |
dc.format.medium | ||
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | Wiley | |
dc.subject | Animals | |
dc.subject | Bone Resorption | |
dc.subject | Cell Differentiation | |
dc.subject | Cell Line | |
dc.subject | Cell Survival | |
dc.subject | Coumestrol | |
dc.subject | Genistein | |
dc.subject | Isoflavones | |
dc.subject | Mice | |
dc.subject | NFATC Transcription Factors | |
dc.subject | Phytoestrogens | |
dc.subject | Polymerase Chain Reaction | |
dc.subject | Proto-Oncogene Proteins c-fos | |
dc.subject | Tumor Necrosis Factor-alpha | |
dc.title | Phytoestrogens directly inhibit TNF-α-induced bone resorption in RAW264.7 cells by suppressing c-fos-induced NFATc1 expression. | |
dc.type | journal-article | |
dc.type | Article | |
plymouth.author-url | http://www.ncbi.nlm.nih.gov/pubmed/21268069 | |
plymouth.issue | 2 | |
plymouth.volume | 112 | |
plymouth.publication-status | Published | |
plymouth.journal | J Cell Biochem | |
dc.identifier.doi | 10.1002/jcb.22935 | |
plymouth.organisational-group | /Plymouth | |
plymouth.organisational-group | /Plymouth/Faculty of Health | |
plymouth.organisational-group | /Plymouth/Faculty of Health/School of Biomedical Sciences | |
plymouth.organisational-group | /Plymouth/Research Groups | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED) | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR | |
plymouth.organisational-group | /Plymouth/Research Groups/Plymouth Institute of Health and Care Research (PIHR) | |
plymouth.organisational-group | /Plymouth/Users by role | |
plymouth.organisational-group | /Plymouth/Users by role/Academics | |
dc.publisher.place | United States | |
dc.identifier.eissn | 1097-4644 | |
dc.rights.embargoperiod | Not known | |
rioxxterms.versionofrecord | 10.1002/jcb.22935 | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.type | Journal Article/Review |