Effects of co-exposure to fluoride and arsenite on transcription levels of bone morphogenetic proteins 2 and runt-related transcription factor 2 genes in bone of rats
10.3760/cma.j.issn.2095-4255.2018.08.003
- VernacularTitle:氟砷联合暴露对大鼠骨组织骨形态发生蛋白2和骨形成相关因子Runt转录因子2 基因转录表达的影响
- Author:
Zixiu QIN
1
;
Hao LI
;
Junwei HU
;
Xing YANG
;
Bingjie WANG
;
Feng HONG
Author Information
1. 贵州医科大学公共卫生学院卫生毒理学教研室 环境污染与疾病监控教育部重点实验室
- Keywords:
Fluoride;
Arsenites;
Bone morphogenetic proteins 2;
Runt-related transcription factor 2;
Rats;
Bones
- From:
Chinese Journal of Endemiology
2018;37(8):612-617
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of chronic fluoride and arsenic co-exposure on bone morphogenetic proteins 2 (BMP-2) and runt-related transcription factor 2 (Runx2) gene expressions of bone tissue in rats. Methods One hundred and sixty 8-week-old clean-grade Wistar rats weighting (200 ± 50) g were randomly divided into 16 groups by weight via the random number table method of 10 rats in each group by 2 × 4 factorial experimental design (half female and half male), and treated with different doses of fluoride, arsenite and fluoride plus arsenite in deionized water (untreated control group with 0.0 mg/kg fluoride and 0.0 mg/kg arsenite; low-, moderate- and high-fluoride groups were supplemented with 5.0, 10.0 and 20.0 mg/kg fluoride and 2.5, 5.0 and 10.0 mg/kg arsenite) for 6 months. Rats were divided into control (F0.0As0.0), low fluorine (F5.0As0.0), moderate fluorine (F10.0As0.0), high fluorine (F20.0As0.0), low arsenic (F0.0As2.5), moderate arsenic (F0.0As5.0), high arsenic (F0.0As10.0), low fluorine and low arsenic (F5.0As2.5), low fluorine and moderate arsenic (F5.0As5.0), low fluorine and high arsenic (F5.0As10.0), moderate fluorine and low arsenic (F10.0As2.5), moderate fluorine and moderate arsenic (F10.0As5.0), moderate fluorine and high arsenic (F10.0As10.0), high fluorine and low arsenic (F20.0As2.5), high fluorine and moderate arsenic (F20.0As5.0), high fluorine and high arsenic (F20.0As10.0) groups. The concentrations of urinary fluoride (UF) and urinary arsenic (UAs) were determined as exposure biomarkers via the fluoride ion selective electrode method and the flame atomic fluorescence method. The mRNA expressions of BMP-2 and Runx2 were measured with quantitive real-time PCR. Results There were no dental fluorosis found in F0.0As0.0, F0.0As2.5, F0.0As5.0 and F0.0As10.0 groups, and there was a dose-response relationship between the occurrence of dental fluorosis and fluoride doses. Under exposure of fluorine and arsenic combined with high dose of fluorine (20.0 mg/kg), with increasing of arsenic exposure doses, the degree of injury of dental fluorosis increased (χ2 = 9.124, P < 0.05). Compared with F0.0As0.0 (0.99 ± 0.08, 0.99 ± 0.07), the mRNA expressions of BMP-2 (1.01 ± 0.07, 1.06 ± 0.06, 1.21 ± 0.05) and Runx2 (1.03 ± 0.04, 1.24 ± 0.03, 1.33 ± 0.10) in F5.0As0.0, F10.0As0.0, F20.0As0.0 groups were increased with increasing of fluoride doses. Fluoride had a significant effect on mRNA expressions of BMP-2 and Runx2 (F=3.067, 2.927, P<0.05). There was a significant interaction between fluoride and arsenic combination and BMP-2 and Runx2 mRNA expression levels (F = 3.817, 4.802, P < 0.05). Conclusion When rat is co-exposed to fluorine and arsenic, fluorine plays a leading role on BMP-2 and Runx2 mRNA expressions, and arsenic is indirectly involved in fluoride-induced bone toxicity; fluorine and arsenic has a antagonistic effect on BMP-2 and Runx2 mRNA expressions.
