The Inverted U-Curve Association of Fluoride and Osteoclast Formation in Mice.
The Inverted U-Curve Association of Fluoride and Osteoclast Formation in Mice.
复制标题
小鼠氟化物与破骨细胞形成的倒 U 形曲线关联。
DOI：
10.1007/s12011-018-1624-3
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发表时间：
2019
影响因子：
3.9
通讯作者：
Pei Junrui
中科院分区：
文献类型：
--
作者：
Yao Yingjie;Ma Yongzheng;Zhong Nan;Pei Junrui
氟对破骨细胞的影响仍存在争议。过去，研究人员认为氟对破骨细胞和成骨细胞形成的影响具有剂量依赖性。然而，我们之前的体外研究表明，氟对破骨细胞的形成有显著不同的影响。为进一步验证体内氟与破骨细胞形成的关系，将60只雄性C57BL/6小鼠随机分为三组，一组饮水中添加氟50和100g/L，另一组不加水。采用离子选择电极法测定骨氟含量，苏木精-伊红(HE)染色评价氟对骨组织的影响。免疫组织化学方法检测抗酒石酸酸性磷酸酶(TRAP)的表达。采用TRAP染色和细胞形态观察相结合的方法鉴定骨组织中的破骨细胞。结果表明，随着氟暴露剂量的增加，各剂量组大鼠骨钙素表达增加，且100 mg/L剂量组碱性磷酸酶表达显著高于50 mg/L剂量组和对照组。3组中以50 mg/L组破骨细胞数最多，其次是100 mg/L组，其次是对照组，后者的破骨细胞数明显少于任何一组。这些结果表明，随着氟暴露水平的增加，氟可以促进骨形成。然而，在氟暴露和破骨细胞形成之间发现了倒U曲线关系，较高剂量的氟化物略微减少了破骨细胞的形成。这项研究的结果可能为理解破骨细胞在氟骨症进展中的作用提供关键的见解。
The effect of fluoride on osteoclasts is still controversial. In the past, researchers thought that the effects of fluoride on osteoclast and osteoblast formation occurred in a dose-dependent pattern. However, our previous in vitro study showed fluoride elicited a notably different effect on osteoclast formation. To further verify the relationship between fluoride and osteoclast formation in vivo, 60 male C57BL/6 mice were randomly divided into three groups: two treatment groups consuming water supplemented with 50 and 100 mg/L of fluoride, and a third control group with nonsupplemented water. Ion selective electrode method analysis was used to detect bone fluoride content, and the effects of fluoride on bone tissue were assessed with hematoxylin and eosin (HE) staining. Additionally, the expression of BGP and ALP were examined by Western blot analysis, and tartrate-resistant acid phosphatase (TRAP) was assessed with immunohistochemistry. Osteoclasts in bone tissue were identified with a combination method of TRAP staining and cell morphology assessment. Results showed increasing expression of BGP among treatment groups as fluoride exposure increased, and ALP expression in the 100 mg/L treatment group was significantly higher than that for both the 50 mg/L treatment and control groups. The number of osteoclasts in the 50 mg/L group was highest amongst the three groups, followed by the 100 mg/L treatment and then by the control group, with the latter showing significantly fewer osteoclasts than in either treatment group. These results suggest that fluoride enhances bone formation at increasing levels of fluoride exposure. However, the inverted U-curve association was found between fluoride exposure and osteoclast formation, with the higher dose of fluoride having slightly reduced osteoclast formation. The results from this study may provide key insights towards understanding the role of osteoclasts in the progression of skeletal fluorosis.