| First Author | Lv YG | Year | 2016 |
| Journal | Biochem Biophys Res Commun | Volume | 479 |
| Issue | 2 | Pages | 372-379 |
| PubMed ID | 27644876 | Mgi Jnum | J:239129 |
| Mgi Id | MGI:5824973 | Doi | 10.1016/j.bbrc.2016.09.083 |
| Citation | Lv YG, et al. (2016) Fluorosis increases the risk of postmenopausal osteoporosis by stimulating interferon gamma. Biochem Biophys Res Commun 479(2):372-379 |
| abstractText | Estrogen deficiency in postmenopausal women frequently activates osteoclasts (OC), accelerates bone resorption, and leads to osteoporosis (OP). Previous studies have demonstrated that interferon gamma (IFNgamma) could increase bone resorption and may be involved in postmenopausal OP. Fluorosis also increased the risk of fractures and dental fluorosis, and fluoride may enhance osteoclast formation and induce osteoclastic bone destruction in postmenopausal women, but the underlying mechanisms are as yet unknown. Here, we show that serum fluoride and IFNgamma levels are negatively correlated with bone mineral density (BMD) in postmenopausal women residing in a fluorotic area. Estrogen suppresses IFNgamma, which is elevated by fluoride, playing a pivotal role in triggering bone loss in estrogen-deficient conditions. In vitro, IFNgamma is inhibited by estrogen treatment and increased by fluoride in Raw264.7 cell, an osteoclast progenitor cell line. In ovariectomized (Ovx) mice, estrogen loss and IFNgamma promote OC activation and subsequent bone loss in vivo. However, IFNgamma deficiency prevents bone loss in Ovx mice even in fluoride conditions. Interestingly, fluoride fails to increase IFNgamma expression in estrogen receptor alpha (ERalpha)-deficient conditions, but not in ERbeta-deficient conditions. These findings demonstrate that fluorosis increases the bone loss in postmenopausal OP through an IFNgamma-dependent mechanism. IFNgamma signaling activates OC and aggravates estrogen deficiency inducing OP. Thus, stimulation of IFNgamma production is a pivotal ''upstream'' mechanism by which fluoride promotes bone loss. Suppression of IFNgamma levels may constitute a therapeutic approach for preventing bone loss. |
