title: Effects of fluoride on expression of bone-specific genes in developing Xenopus laevis larvae.
abstract: The effect of fluoride treatment on the expression of a panel of osteogenic and stress markers in Stage 55 premetamorphic Xenopus larvae was examined at the precise onset of replacement of the larval cartilaginous skeleton with bone. A dosing regimen of 10 mmol/L sodium fluoride over 8 days was followed, during which time larvae developed to Stage 58, when the process of progressive ossification takes place in the vertebral column and membranous bones of the skull, pelvic, and pectoral girdles and portions of the appendicular skeleton. Markers of bone formation, including COL1A1, the transcription factors Osterix, RUNX2-II, and matrix metalloproteinases MMP1 and MMP13, decreased relative to age-matched controls, though the osteoblast marker BGLAP was not significantly altered. Expression of the pro-osteoclastogenic factor RANKL decreased, whereas expression of the anti-osteoclastogenic factor osteoprotegerin increased. Altered expression of oxidative stress markers, with the exception of superoxide dismutase, was generally not observed. These data demonstrate the potent effects of fluoride on the expression of factors required for osteoblast and osteoclast differentiation, as well as on the expression of osteoblast products, including MMP1 and collagen. Importantly, these effects were observed in the absence of significant changes in the expression of oxidative stress markers. The results provide the first molecular insights into the mechanisms underlying skeletal fluorosis in a whole organism developmental model.
authors.affiliation: College of Medicine, University of Saskatchewan, Health Sciences Building, Saskatoon, Canada.
authors.forename: Manoj
authors.initials: M
authors.lastname: Nair
authors.forename: Zachery R
authors.initials: ZR
authors.lastname: Belak
authors.forename: Nick
authors.initials: N
authors.lastname: Ovsenek
mesh_terms: D000818:Animals; D001846:Bone Development / Q000235:genetics*; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D005819:Genetic Markers; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D050958:HSP47 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D007814:Larva / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D012969:Sodium Fluoride / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000254:growth & development*
chemical_list: D005819:Genetic Markers; D050958:HSP47 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; D012969:Sodium Fluoride; D003094:Collagen; D002374:Catalase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase