- NaF induced NETs formation.
- NaF caused imbalance between ROS and antioxidant system.
- NaF induced NETs formation via ROS, ERK, and p38 signaling pathways.
In recent years, numerous studies paid more attention to the molecular mechanisms associated with fluoride toxicity. However, the detailed mechanisms of fluoride immunotoxicity in bovine neutrophils remain unclear. Neutrophil extracellular traps (NETs) is a novel immune mechanism of neutrophils. We hypothesized that sodium fluoride (NaF) can trigger NETs activation and release, and investigate the related molecular mechanisms during the process. We exposed peripheral blood neutrophils to 1 mM NaF for 120 min in bovine neutrophils. The results showed that NaF exposure triggered NET-like structures decorated with histones and granule proteins. Quantitative measurement of NETs content correlated positively with the concentration of NaF. Mechanistically, NaF exposure increased reactive oxygen species (ROS) levels and phosphorylation levels of ERK, p38, whereas inhibiting the activities of superoxide dismutase (SOD) and catalase (CAT) compared with control neutrophils. NETs formation is induced by NaF and this effect was inhibited by the inhibitors diphenyleneiodonium chloride (DPI), U0126 and SB202190. Our findings described the potential importance of NaF-triggered NETs related molecules, which might help to extend the current understanding of NaF immunotoxicity.
The dose-time effects of fluoride on the expression and DNA methylation level of the promoter region of BMP-2 and BMP-7 in rats.
Highlights Fluoride has a dose-time effect on Bone Morphogenetic Protein-2 expression. Fluoride increases the expression of Bone Morphogenetic Protein-2 and 7. DNA methylation may be involved in fluoride regulation of target protein expression. Skeletal fluorosis is a chronic metabolic bone disease caused by excessive exposed to fluoride. Recent studies have
Anabolic effects of fluoride on bone
Fluoride exerts a biphasic action at the level of osteoblasts, on bone mineral, on bone structure and function, and in the treatment of osteoporosis. At low circulating concentrations, skeletal uptake of fluoride is limited and the effects are beneficial. At higher concentrations and greater skeletal uptake, fluoride may cause the
The role of TGFß receptor 1-smad3 signaling in regulating the osteoclastic mode affected by fluoride.
Highlights Fluoride upregulated 303 miRNAs expression and downregulated 61 miRNAs. Fluoride exhibited biphasic effect on osteoclast viability, formation and function. Fluoride indicated little effect on expression of RANK protein. SB431542 inhibited or aggravated fluoride-regulating osteoclast mode. Stimulation of fluoride on Smad3 expression exhibited dose-dependent manner. Studies that have focused on
Sodium fluoride induced skeletal muscle changes: Degradation of proteins and signaling mechanism.
Highlights Sodium fluoride at low concentrations causes excessive proliferation of C2C12 myoblasts. Sodium fluoride causes production ROS and inflammatory cytokines in myoblasts and differentiating myotubes. Sodium fluoride at low concentrations causes hypertrophy of the differentiating myoblasts and activates PI3K/AKT signaling pathway. Ubiquitin-proteasome pathway plays a major role in sodium
Fluoride regulates the expression of extracellular matrix HSPG and related signaling pathways FGFR3 and Ihh/PTHrP feedback loop during endochondral ossification.
Highlights Fluoride promotes the expression of HSPG in growth plate of rats during endochondral ossification. Fluoride activates FGFR3 signaling pathway during endochondral ossification. Fluoride inhibits Ihh/PTHrP feedback loop during endochondral ossification. Abstract Fluoride promotes the expression of HSPG in growth plate of rats during endochondral ossification. Fluoride activates FGFR3 signaling pathway
Related Studies :
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.
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.
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.
Related FAN Content :