Calcium supplementation attenuates fluoride-induced bone injury via PINK1/Parkin-mediated mitophagy and mitochondrial apoptosis in mice.
J Hazard Mater
; 465: 133411, 2024 03 05.
Article
em En
| MEDLINE
| ID: mdl-38181596
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Mitofagia
/
Fluoretos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J Hazard Mater
Ano de publicação:
2024
Tipo de documento:
Article