title: Bone response to fluoride exposure is influenced by genetics.
abstract: Genetic factors influence the effects of fluoride (F) on amelogenesis and bone homeostasis but the underlying molecular mechanisms remain undefined. A label-free proteomics approach was employed to identify and evaluate changes in bone protein expression in two mouse strains having different susceptibilities to develop dental fluorosis and to alter bone quality. In vivo bone formation and histomorphometry after F intake were also evaluated and related to the proteome. Resistant 129P3/J and susceptible A/J mice were assigned to three groups given low-F food and water containing 0, 10 or 50 ppmF for 8 weeks. Plasma was evaluated for alkaline phosphatase activity. Femurs, tibiae and lumbar vertebrae were evaluated using micro-CT analysis and mineral apposition rate (MAR) was measured in cortical bone. For quantitative proteomic analysis, bone proteins were extracted and analyzed using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS), followed by label-free semi-quantitative differential expression analysis. Alterations in several bone proteins were found among the F treatment groups within each mouse strain and between the strains for each F treatment group (ratio ≥1.5 or ≤0.5; p<0.05). Although F treatment had no significant effects on BMD or bone histomorphometry in either strain, MAR was higher in the 50 ppmF 129P3/J mice than in the 50 ppmF A/J mice treated with 50 ppmF showing that F increased bone formation in a strain-specific manner. Also, F exposure was associated with dose-specific and strain-specific alterations in expression of proteins involved in osteogenesis and osteoclastogenesis. In conclusion, our findings confirm a genetic influence in bone response to F exposure and point to several proteins that may act as targets for the differential F responses in this tissue.
authors.affiliation: Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil.
authors.forename: Cláudia A N
authors.initials: CA
authors.lastname: Kobayashi
authors.affiliation: Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil.
authors.forename: Aline L
authors.initials: AL
authors.lastname: Leite
authors.affiliation: Centro de Ciências da Saúde, Universidade do Sagrado Coração, Bauru, SP, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Peres-Buzalaf
authors.affiliation: Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil.
authors.forename: Juliane G
authors.initials: JG
authors.lastname: Carvalho
authors.affiliation: Department of Oral Biology, College of Dental Medicine, Georgia Regents University, Augusta, Georgia, United States.
authors.forename: Gary M
authors.initials: GM
authors.lastname: Whitford
authors.affiliation: Department of Pediatric Dentistry, The Carolina Center for Genome Sciences, School of Dentistry, University of North Carolina, Chapel Hill, North Carolina, United States.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Everett
authors.affiliation: Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
authors.forename: Walter L
authors.initials: WL
authors.lastname: Siqueira
authors.affiliation: Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil.
authors.forename: Marília A R
authors.initials: MA
authors.lastname: Buzalaf
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000566:Amelogenesis / Q000187:drug effects* / Q000235:genetics*; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D024042:Collagen Type I / Q000378:metabolism; D005459:Fluorides / Q000494:pharmacology*; D009050:Fluorosis, Dental / Q000517:prevention & control; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects* / Q000235:genetics*; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects; D010641:Phenotype; D040901:Proteomics; D013045:Species Specificity
chemical_list: D024042:Collagen Type I; D000469:Alkaline Phosphatase; D005459:Fluorides