Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & National Health Commission (23618504), Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, 150081, Heilongjiang Province, China.
Biol Trace Elem Res. 2019 Oct;191(2):419-425. doi: 10.1007/s12011-018-1624-3. Epub 2019 Jan 2.
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.
氟化物对破骨细胞的影响仍存在争议。过去，研究人员认为氟化物对破骨细胞和成骨细胞形成的影响呈剂量依赖性模式。然而，我们之前的体外研究表明，氟化物对破骨细胞形成的影响明显不同。为了进一步验证氟化物与体内破骨细胞形成的关系，将 60 只雄性 C57BL/6 小鼠随机分为三组：两组分别饮用添加 50 和 100mg/L 氟化物的水，第三组为不添加氟化物的水。采用离子选择性电极法检测骨氟含量，用苏木精-伊红（HE）染色评估氟化物对骨组织的影响。此外，通过 Western blot 分析检测 BGP 和 ALP 的表达，通过免疫组织化学法检测抗酒石酸酸性磷酸酶（TRAP）。通过 TRAP 染色和细胞形态评估的组合方法鉴定骨组织中的破骨细胞。结果表明，随着氟化物暴露的增加，治疗组中 BGP 的表达增加，100mg/L 治疗组中 ALP 的表达明显高于 50mg/L 治疗组和对照组。三组中，50mg/L 组的破骨细胞数量最高，其次是 100mg/L 治疗组，然后是对照组，后者的破骨细胞数量明显少于治疗组。这些结果表明，氟化物在氟化物暴露增加的情况下增强了骨形成。然而，氟化物暴露与破骨细胞形成之间发现了倒 U 型关联，高剂量的氟化物略微减少了破骨细胞的形成。本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重要的见解。
