Skeletal fluorosis is a chronic metabolic bone disease caused by excessive exposed to fluoride. Recent studies have shown that fluoride causes abnormal bone metabolism through disrupting the expression of Bone Morphogenetic Proteins (BMPs). However, the relationship between fluoride and BMPs is not fully understood, and the mechanism of fluoride on BMPs expression is still unclear. This study investigated the dose-time effects of fluoride on BMP-2 and BMP-7 levels and DNA methylation status of the promoter regions of these two genes in peripheral blood of rats. Eighty Wistar male rats were randomly divided into four groups and treated for 1 month and 3 months with distilled water (control), 25 mg/L, 50 mg/L or 100 mg/L of sodium fluoride (NaF). Rats exposed to fluoride had higher protein expression of BMP-2 and BMP-7 in plasma at 1 month and 3 months. An increase in BMP-2 expression was also observed with an increase of fluoride exposure time. Significant hypomethylation was observed in 2 CpG sites (CpGs) of BMP-2 and 1 CpG site of BMP-7 promoter regions in the fluoride treatment groups. It concludes that fluoride has a dose-response effect on BMP-2 in fluorosis rats, and fluoride-induced hypomethylation of specific CpGs may play an essential role in the regulation of BMP-2 and BMP-7 expression in rats.

骨骼氟中毒是由于过度暴露于氟化物引起的慢性代谢性骨疾病。最近的研究表明，氟化物通过破坏骨形态发生蛋白（BMP）的表达而引起异常的骨骼代谢。然而，氟化物与BMPs之间的关系尚不完全清楚，氟化物对BMPs表达的机制仍不清楚。本研究调查了氟对大鼠外周血中BMP-2和BMP-7水平以及这两个基因启动子区域DNA甲基化状态的剂量-时间效应。将80只Wistar雄性大鼠随机分为四组，分别用蒸馏水（对照组），25 mg / L，50 mg / L或100 mg / L氟化钠（NaF）处理1个月和3个月。暴露于氟化物的大鼠在1个月和3个月时血浆中BMP-2和BMP-7的蛋白表达较高。随着氟暴露时间的增加，还观察到BMP-2表达的增加。在氟化物治疗组中，在BMP-2的2个CpG位点（CpGs）和BMP-7启动子区域的1个CpG位点中观察到明显的低甲基化。结论是氟化物对氟中毒大鼠的BMP-2具有剂量反应作用，氟化物诱导的特定CpGs甲基化可能在大鼠BMP-2和BMP-7表达的调节中起重要作用。