Abstract：
Excessive consumption of fluoride can cause skeletal fluorosis. Mitophagy has been identified as a novel target for bone disorders. Meanwhile, calcium supplementation has shown great potential for mitigating fluoride-related bone damage. Hence, this study aimed to elucidate the association between mitophagy and skeletal fluorosis and the precise mechanisms through which calcium alleviates these injuries. A 100 mg/L sodium fluoride (NaF) exposure model in Parkin knockout (Parkin-/-) mice and a 100 mg/L NaF exposure mouse model with 1% calcium carbonate (CaCO3) intervention were established in the current study. Fluoride exposure caused the impairment of mitochondria and activation of PTEN-induced putative kinase1 (PINK1)/E3 ubiquitin ligase Park2 (Parkin)-mediated mitophagy and mitochondrial apoptosis in the bones, which were restored after blocking Parkin. Additionally, the intervention model showed fluoride-exposed mice exhibited abnormal bone trabecula and mechanical properties. Still, these bone injuries could be effectively attenuated by adding 1% calcium to their diet, which reversed fluoride-activated mitophagy and apoptosis. To summarize, fluoride can activate bone mitophagy through the PINK1/Parkin pathway and mitochondrial apoptosis. Parkin-/- and 1% calcium provide protection against fluoride-induced bone damage. Notably, this study provides theoretical bases for the prevention and therapy of animal and human health and safety caused by environmental fluoride contamination.
摘要：
过量消耗氟化物会导致氟骨症。线粒体自噬已被确定为骨骼疾病的新靶标。同时,补充钙已显示出减轻氟化物相关骨损伤的巨大潜力.因此，本研究旨在阐明线粒体自噬与氟骨症之间的关联，以及钙减轻这些损伤的确切机制。本研究建立了Parkin基因敲除(Parkin-/-)小鼠100mg/L氟化钠(NaF)暴露模型和1%碳酸钙(CaCO3)干预的100mg/LNaF暴露小鼠模型。氟化物暴露导致线粒体受损和PTEN诱导的推定激酶1（PINK1）/E3泛素连接酶Park2（Parkin）介导的线粒体自噬和线粒体凋亡的激活，封锁Parkin后恢复了.此外,干预模型显示，氟暴露小鼠骨小梁和力学性能异常。尽管如此，通过在他们的饮食中添加1%的钙可以有效地减轻这些骨骼损伤，逆转氟化物激活的线粒体自噬和细胞凋亡。总结一下,氟可以通过PINK1/Parkin通路激活骨线粒体自噬和线粒体凋亡。Parkin-/-和1％的钙可防止氟化物引起的骨损伤。值得注意的是,本研究为环境氟化物污染对动物和人类健康安全的防治提供了理论依据。
