Fluoride decreased osteoclastic bone resorption through the inhibition of NFATc1 gene expression

• DOI: 10.1002/tox.21784
• Publication Date: 2012-05-20T14:52:46Z
• Authors: Junrui Pei; Bingyun Li; Yanhui Gao; Yudan Wei; Lingwang Zhou; Hongju Yao; Jing Wang; Dianjun Sun
• Keywords: Cathepsin K; NFAT

Over the past two decades, fluoride effects on osteoclasts have been evaluated; however, its molecular mechanisms remain unclear. In this study, we investigated effect of osteoclast formation, function, and regulation using formed from mice bone marrow macrophages treated with receptor activator NF‐κB ligand macrophage colony‐stimulating factor. Our data showed that levels ≤ 8 mg/L had no formation; it significantly reduced resorption at 0.5 mg/L. Fluoride activity occurred through inhibition nuclear factor active T cells (NFAT) c1 expression. Furthermore, expression downstream genes, including dendritic cell‐specific transmembrane protein, c‐Src, d2 isoform vacuolar (H+) ATPase v0 domain, matrix metalloproteinase 9, cathepsin K were decreased, leading to impaired acidification, secretion proteolytic enzymes, decreased resorption. summary, our results suggested has different roles in formation function. did not impact newly osteoclasts. The mechanism action may involve NFATc1 genes. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 588–595, 2014.