- Effects of fluoride on the transcriptome and metabolome in BMSCs were studied.
- Fluoride inhibited lysosomal function.
- Glutathione metabolism was the hub affected metabolic processes in fluoride -treated BMSCs.
- Palmitic acid and prostaglandin metabolisms were associated with lysosomal pathway in fluoride-treated BMSCs.
Fluoride has received much attention for its predominant bone toxicity in the human body. However, the toxic mechanism of bone injury caused by fluoride exposure remains largely unclear. Bone marrow mesenchymal stem cells (BMSCs) are widely used as model cells for evaluating bone toxicity after environmental toxicant exposure. In this study, BMSCs were exposed to fluoride at 1, 2, and 4 mM for 24 h, and fluoride significantly inhibited cell viability at 2 and 4 mM. A multiomics analysis combining transcriptomics with metabolomics was employed to detect alterations in genes and metabolites in BMSCs treated with 2 mM fluoride. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of transcriptomics profiles identified “lysosomes” as the top enriched pathway, which was severely damaged by fluoride exposure. Lysosomal damage was indicated by decreases in the expression of lysosomal associated membrane protein 2 (LAMP 2) and cathepsin B (CTSB) as well as an increase in pH. Upregulation of the lysosome-related genes Atp6v0b and Gla was observed, which may be attributed to a compensatory lysosomal biogenesis transcriptional response. Interestingly, inhibition of glutathione metabolism was observed in fluoride-treated BMSCs at the metabolomic level. Moreover, an integrative analysis between altered genes, metabolites and lysosome signaling pathways was conducted. Palmitic acid, prostaglandin C2, and prostaglandin B2 metabolites were positively associated with Atp6v0b, a lysosome-related gene. Overall, our results provide novel insights into the mechanism responsible for fluoride-induced bone toxicity.
*Original abstract online at https://www.sciencedirect.com/science/article/pii/S0147651322005127?via%3Dihub
[Effects on expression of osteogenesisgene in the osteoblast with endoplasmic reticulum stress induced by fluoride].
OBJECTIVE: To explore the gene expressions of endoplasmic reticulum stress and differentiation in osteoblast treated by excess fluoride. METHODS: Using primary cultured human osteoblasts for fluorosis model in vitro, apoptosis was inspected by flow cytometer, and RNA was extracted for examination of the unfolded protein response and bone differentiation genes. RESULTS: Fluoride
Effect of fluoride on expression of pura gene and CaM gene in newborn rat osteoblasts.
To explore the effect of fluoride (F) on the expression of purine-rich element-binding protein (PURA) gene and calmodulin (CaM) gene in osteoblasts of newborn rats, parietal calvaria bone osteoblast cultures of 48-hr-old rats were treated for 48 hr with sodium fluoride (NaF) at concentrations of 0 (control), 0.5, 2, and
Preliminary screening of fluorine-stained osteoblastic apoptosis-related microRNA.
This article has been accepted for publication and undergone full peer review but has not been through the copy editing, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/ar.24709. Endemic fluorosis is a chronic systemic
Fluorosilicic acid induces DNA damage and oxidative stress in bone marrow mesenchymal stem cells.
Highlights Fluorosilicic acid is the most used additive for water fluoridation. Dental fluorosis can be caused by fluorosilicic acid present in drinking water. DNA damage was caused by fluorosilicic acid in mesenchymal stem cells. Fluorosilicic acid altered bone mineralization in mesenchymal stem cells. DNA damage caused by fluorosilicic acid
Role of fluoride induced epigenetic alterations in the development of skeletal fluorosis.
Highlights WGBS data depict altered methylation of genes regulating bone development pathways. Fluoride causes diminished expression of BMP1, METAP2, MMP11 and BACH1 genes. These genes play a critical role in catabolic process of skeletal development. DNA hypermethylation of these critical genes thus promote skeletal fluorosis. Fluoride is an essential trace element
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Skeletal Fluorosis: The Misdiagnosis Problem
It is a virtual certainty that there are individuals in the general population unknowingly suffering from some form of skeletal fluorosis as a result of a doctor's failure to consider fluoride as a cause of their symptoms. Proof that this is the case can be found in the following case reports of skeletal fluorosis written by doctors in the U.S. and other western countries. As can be seen, a consistent feature of these reports is that fluorosis patients--even those with crippling skeletal fluorosis--are misdiagnosed for years by multiple teams of doctors who routinely fail to consider fluoride as a possible cause of their disease.
Fluoride & Osteoarthritis
While the osteoarthritic effects that occurred from fluoride exposure were once considered to be limited to those with skeletal fluorosis, recent research shows that fluoride can cause osteoarthritis in the absence of traditionally defined fluorosis. Conventional methods used for detecting skeletal fluorosis, therefore, will fail to detect the full range of people suffering from fluoride-induced osteoarthritis.
As demonstrated by the studies below, skeletal fluorosis may produce adverse symptoms, including arthritic pains, clinical osteoarthritis, gastrointestinal disturbances, and bone fragility, before the classic bone change of fluorosis (i.e., osteosclerosis in the spine and pelvis) is detectable by x-ray. Relying on x-rays, therefore, to diagnosis skeletal fluorosis will invariably fail to protect those individuals who are suffering from the pre-skeletal phase of the disease. Moreover, some individuals with clinical skeletal fluorosis will not develop an increase in bone density, let alone osteosclerosis, of the spine. Thus, relying on unusual increases in spinal bone density will under-detect the rate of skeletal fluoride poisoning in a population.
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