title: Sodium fluoride induces apoptosis and alters bcl-2 family protein expression in MC3T3-E1 osteoblastic cells.
abstract: Chronic excessive fluoride intake is known to be toxic and can lead to fluorosis and bone pathologies. However, the cellular mechanisms underlying NaF-induced cytotoxicity in osteoblasts are not well understood. The objectives of this study were to determine the effects of fluoride treatment on MC3T3-E1 osteoblastic cell viability, cell cycle analysis, apoptosis and the expression levels of bcl-2 family members: bcl-2 and bax. MC3T3-E1 cells were treated with 10(-5); 5 × 10(-5); 10(-4); 5 × 10(-4) and 10(-3)M NaF for up to 48 h. NaF was found to reduce cell viability in a temporal and concentration dependent manner and promote apoptosis even at low concentrations (10(-5)M). This increased apoptosis was due to alterations in the expression of both pro-apoptotic bax and anti-apoptotic bcl-2. The net result was a decrease in the bcl-2/bax ratio which was found at both the mRNA and protein levels. Furthermore, we also noted that NaF-induced S-phase arrest during the cell cycle of MC3T3-E1 cells. These data suggest that fluoride-induced osteoblast apoptosis is mediated by direct effects of fluoride on the expression of bcl-2 family members.
authors.affiliation: College of Veterinary Medicine, China Agricultural University, 100193 Beijing, China.
authors.forename: Shiyong
authors.initials: S
authors.lastname: Yang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.forename: Colin
authors.initials: C
authors.lastname: Farquharson
authors.forename: Rashad
authors.initials: R
authors.lastname: Alkasir
authors.forename: Mohammad
authors.initials: M
authors.lastname: Zahra
authors.forename: Gaixian
authors.initials: G
authors.lastname: Ren
authors.forename: Bo
authors.initials: B
authors.lastname: Han
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D012969:Sodium Fluoride / Q000494:pharmacology*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D012969:Sodium Fluoride