Abstract
Endemic fluorosis is a serious problem in public health, affecting thousands of people. Abnormal proliferation and activation of osteoblasts in skeletal fluorosis lesions play a leading role and osteoblast proliferation is finely regulated by the cell cycle. There are a few reports on fluoride-induced DNA methylation. However, the role of DNA methylation of the cyclin/cyclin-dependent kinase (CDK)/cyclin-dependent kinase inhibitor (CKI) regulatory network in skeletal fluorosis has not been investigated. We used a population study and in vitro experiment to explore the relationship between the pathogenesis of skeletal fluorosis and methylation of Cyclin d1/CDK4/p21. The results showed a positive relationship between fluoride exposure and expression of Cyclin d1/CDK4, and a negative relationship between fluoride exposure and expression of P21. Hypermethylation of p21 was found in the fluoride-exposed population, and low expression of p21 attributed to promoter hypermethylation was confirmed in vitro. However, no changes in methylation levels of Cyclin d1 and CDK4 genes were observed in the population exposed to fluoride and NaF-treated osteoblasts. These results show that methylation of p21 gene has a significant impact on the proliferation of osteoblasts during the development of skeletal fluorosis. The present study was a first attempt to link the methylation of the Cyclin d1/CDK4/p21 regulatory network with osteoblast proliferation in skeletal fluorosis.
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Prolactin rs1341239 T allele may have protective role against the brick tea type skeletal fluorosis
OBJECTIVE: Prolactin (PRL) has been reported to be associated with increased bone turnover, and increased bone turnover is also a feature of skeletal fluorosis (SF). Autocrine/paracrine production of PRL is regulated by the extrapituitary promoter and a polymorphism in the extrapituitary PRL promoter at -1149 (rs1341239) is associated with disturbances
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The spectrum of radiographic bone changes in children with fluorosis
Painful, crippling deformities in Tanzanian children from an area of endemic fluorosis are reported. Excessive fluoride ingestion in pregnant women may possibly poison and alter enzyme and hormonal systems in the fetus causing disturbances to osteoid formation and mineralization. Knock-knees, bowlegs, and saber shins develop when walking begins. Combinations of osteomalacia, osteoporosis,
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[Qualitative and quantitative variation of serum proteins in fluorosis patients].
Comparison between patients with occupational fluorosis, a group of healthy workers, and a sample from the general population revealed differences in concentrations of some polymorphic serum proteins. These differences depended on phenotypes of patients. TF 1-2, PI 1-2, and HP 2-1 patients exhibited a decreased concentration of transferrin (TF), a
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Comparison of two village primary schools in northern Tanzania affected by fluorosis
High fluoride levels in drinking water sources are a problem throughout the East African Rift Valley and can lead to dental fluorosis (DF) and skeletal fluorosis (SF) in exposed local populations. Two villages in the Hai District of northern Tanzania in which fluoride has been identified as a problem were
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The relationship between Alu I polymorphisms in the calcitonin receptor gene and fluorosis endemic to Chongqing, China
OBJECTIVE: This study explored the association between an Alu I polymorphism at position 1,377 of the calcitonin receptor (CTR) gene and endemic fluorosis. SUBJECTS AND METHODS: A case-control study of 321 participants was conducted in regions with high fluorosis rates (Wushan and Fengjie counties) and those without high fluorosis rates (Yubei
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Factors which increase the risk for skeletal fluorosis
The risk for developing skeletal fluorosis, and the course the disease will take, is not solely dependent on the dose of fluoride ingested. Indeed, people exposed to similar doses of fluoride may experience markedly different effects. While the wide range in individual response to fluoride is not yet fully understood, the following are some of the factors that are believed to play a role.
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"Pre-Skeletal" Fluorosis
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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Fluoridation, Dialysis & Osteomalacia
In the 1960s and 1970s, doctors discovered that patients receiving kidney dialysis were accumulating very high levels of fluoride in their bones and blood, and that this exposure was associated with severe forms of osteomalacia, a bone-softening disease that leads to weak bones and often excruciating bone pain. Based on
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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.
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Skeletal Fluorosis & Individual Variability
One of the common fallacies in the research on skeletal fluorosis is the notion that there is a uniform level of fluoride that is safe for everyone in the population. These "safety thresholds" have been expressed in terms of (a) bone fluoride content, (b) daily dose, (c) water fluoride level, (d) urinary fluoride level, and (e) blood fluoride level. The central fallacy with each of these alleged safety thresholds, however, is that they ignore the wide range of individual susceptibility in how people respond to toxic substances, including fluoride.
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