title: Fluoride decreased osteoclastic bone resorption through the inhibition of NFATc1 gene expression.
abstract: Over the past two decades, fluoride effects on osteoclasts have been evaluated; however, its molecular mechanisms remain unclear. In this study, we investigated the effect of fluoride on osteoclast formation, function, and regulation using osteoclasts formed from mice bone marrow macrophages treated with the receptor activator of NF-κB ligand and macrophage colony-stimulating factor. Our data showed that fluoride levels ≤ 8 mg/L had no effect on osteoclast formation; however, it significantly reduced osteoclast resorption at 0.5 mg/L. Fluoride activity on bone resorption occurred through the inhibition of nuclear factor of active T cells (NFAT) c1 expression. Furthermore, the expression of its downstream genes, including the dendritic cell-specific transmembrane protein, c-Src, the d2 isoform of vacuolar (H+) ATPase v0 domain, matrix metalloproteinase 9, and cathepsin K were decreased, leading to impaired osteoclast acidification, reduced secretion of proteolytic enzymes, and decreased bone resorption. In summary, our results suggested that fluoride has different roles in osteoclast formation and function. Fluoride ≤ 8 mg/L did not impact osteoclast formation; however, it significantly decreased the resorption activity of newly formed osteoclasts. The molecular mechanism of fluoride action may involve inhibition of NFATc1 and its downstream genes.
authors.affiliation: Key Laboratory of Etiologic Epidemiology, Ministry of Health (23618104), Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, Heilongjiang Province, People's Republic of China, >
authors.forename: Junrui
authors.initials: J
authors.lastname: Pei
authors.forename: Bingyun
authors.initials: B
authors.lastname: Li
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Gao
authors.forename: Yudan
authors.initials: Y
authors.lastname: Wei
authors.forename: Lingwang
authors.initials: L
authors.lastname: Zhou
authors.forename: Hongju
authors.initials: H
authors.lastname: Yao
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Dianjun
authors.initials: D
authors.lastname: Sun
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000503:physiopathology*; D000081247:CSK Tyrosine-Protein Kinase; D056657:Cathepsin K / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D005459:Fluorides / Q000009:adverse effects*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; D056657:Cathepsin K; C534132:Ctsk protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; C542312:Atp6v0d2 protein, mouse; D025262:Vacuolar Proton-Translocating ATPases; D005459:Fluorides