Sodium fluoride induces apoptosis and alters bcl-2 family protein expression in MC3T3-E1 osteoblastic cells.
Sodium fluoride induces apoptosis and alters bcl-2 family protein expression in MC3T3-E1 osteoblastic cells.
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DOI：
10.1016/j.bbrc.2011.06.094
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发表时间：
2011-07
影响因子：
3.1
通讯作者：
Shiyong Yang;Zhi Wang;C. Farquharson;Rashad Alkasir;Mohammadalipour Zahra;G. Ren;B. Han
中科院分区：
文献类型：
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作者：
Shiyong Yang;Zhi Wang;C. Farquharson;Rashad Alkasir;Mohammadalipour Zahra;G. Ren;B. Han
众所周知，长期过量摄入氟化物是有毒的，可能会导致氟中毒和骨骼病理。然而，氟化钠诱导成骨细胞毒性的细胞机制还不是很清楚。本研究旨在探讨氟对MC3T3-E1成骨细胞活力、细胞周期分析、细胞凋亡及bcl2家族成员bcl2、bax表达水平的影响。用10−5、5×10−5、10−4、5×10−4和10−3M NaF处理MC3T3-E1细胞48h。发现NaF以时间和浓度依赖的方式降低细胞存活率，并在低浓度(10−，5M)时促进细胞凋亡。细胞凋亡率的增加是由于促凋亡的bax和抗凋亡的bcl2的表达发生了变化。最终结果是bcl2/bax比值下降，这一比值在mRNA和蛋白水平上都存在。此外，我们还注意到NaF诱导MC3T3-E1细胞周期中的S期停滞。这些结果表明，氟诱导的成骨细胞凋亡是由氟对bcl2家族成员表达的直接影响所介导的。
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; 5×10−4and 10−3M NaF for up to 48h. NaF was found to reduce cell viability in a temporal and concentration dependent manner and promote apoptosis even at low concentrations (10−5M). 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.