Abstract

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.

• Related Studies :

  • Effects of fluoride on the proliferation and activation of osteoblasts by regulating methylation of the DNA repair genes MGMT and MLH1.

    Introduction Fluoride can induce the proliferation and activation of osteoblasts, resulting in skeletal fluorosis progression; however, the specific mechanism is unclear. Methods Cell proliferation was examined using the MTT assay. Flow cytometry was performed to detect the cell cycle distribution. Alkaline phosphatase (ALP) was calculated to evaluate bone formation and turnover. Gene methylation

  • Fluoride-mediated apoptosis and disordering of cell cycle distributions during in vitro organ culture of mouse fetal long bones.

    Effects of fluoride (as NaF) on cell cycle, DNA content, and apoptosis of mouse fetal long bone cultures were examined and analyzed by flow cytometry (FCM). The results showed that NaF at 2.5–5.0 µg/mL (2.5–5.0 ppm) had only slight effects on the DNA content and cell cycle distributions. At 10.0

  • 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

  • Distribution of Fluoride in Plasma, Brain, and Bones and Associated Oxidative Damage After Induced Chronic Fluorosis in Wistar Rats.

    The study was aimed to determine fluoride levels in plasma, brain, and bones of Wistar rats following chronic administration of fluoride at different dose levels and the consequent oxidative damage inflicted in these tissues. Brain histomorphology and bone radiographs were also evaluated to assess the extent of damage in these

  • Association Between Antioxidant Nutrients, Oxidative Stress-Related Gene Polymorphism and Skeletal Fluorosis in Guizhou, China.

    Background: Oxidative stress plays an important role in the pathogenesis of endemic fluorosis. We analyzed associations between oxidative stress-related gene polymorphisms (PON1 rs662, CAT rs769217, rs2300182, and SOD2 rs11968525) and skeletal fluorosis, and examined potential gene–environment interactions with dietary vitamin C, vitamin E, zinc, and selenium intake. Methods: A cross-sectional study

• Related FAN Content :

  • "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.

  • 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.

  • Variability in Radiographic Appearance of Skeletal Fluorosis

    Osteosclerosis (dense bone) is the bone change typically associated with skeletal fluorosis, particularly in the axial skeleton (spine, pelvis, and ribs). Research shows, however, that skeletal fluorosis produces a spectrum of bone changes, including osteomalacia, osteoporosis, exostoses, changes resulting from secondary hyperparathyroidism, and combinations thereof. Although the reason for this radiographic variability is not yet fully understood, it is believed to relate to the dose of fluoride consumed, the individual's nutritional status, exposure to aluminum, genetic susceptibility, presence of kidney disease, and area of the skeleton examined.

  • Fluoride & Osteomalacia

    One of fluoride's most well-defined effects on bone tissue is it's ability to increase the osteoid content of bone. Osteoid is unmineralized bone tissue. When bones have too much of it, they become soft and prone to fracture -- a condition known as osteomalacia. As shown below, fluoride has repeatedly been