Fluoride promotes viability and differentiation of osteoblast-like Saos-2 cells via BMP/Smads signaling pathway.

The BMP/Smad signaling pathway plays an important role in the viability and differentiation of osteoblast; however, it is not clear whether this pathway is involved in the fluoride-induced osteoblast differentiation. In this study, we investigated the role of BMP/Smad signaling pathway in fluoride-induced osteoblast-like Saos-2 cells differentiation. Cells were exposed to fluoride of different concentrations (0, 0.1, 0.2, 0.4, 0.8, and 1.6 mM), and cell proliferation was determined using WST assays. The expression of osteoblast marker genes such as osteocalcin (BGP) and bone alkaline phosphatase (BALP) were detected by qRT-PCR. We found that fluoride enhanced the proliferation of Saos-2 cells in a dose-dependent manner and 0.2 mM of fluoride resulted in a higher expression of osteoblast marker genes. In addition, immunofluorescence analysis showed that the promotion effects of 0.2 mM of fluoride on Saos-2 cells differentiation were associated with the activation of the BMP/Smad pathway. Expression of phosphorylated Smad1/5(p-Smad1/5) was higher in cells exposed to 0.2 mM of fluoride. Plasmid expression vectors encoding the short hairpin RNA (shRNA) targeting Smad4 gene were used to block the BMP/Smad pathway, which resulted in a significantly reduced expression of BGP and BALP as well as their corresponding mRNA. The mRNA levels after transfection remained low even in the presence of fluoride. The present results reveal that BMP/Smad signaling pathway was altered during the period of osteogenesis, and that the activities of p-Smad1/5 were required for Saos-2 cells viability and differentiation induced by fluoride.

A national cross-sectional study on effects of fluoride-safe water supply on the prevalence of fluorosis in China.

OBJECTIVE: To assess the effects of provided fluoride-safe drinking-water for the prevention and control of endemic fluorosis in China. DESIGN: A national cross-sectional study in China. SETTING: In 1985, randomly selected villages in 27 provinces (or cities and municipalities) in 5 geographic areas all over China. PARTICIPANTS: Involved 81 786 children aged from 8 to 12 and 594 698 adults aged over 16. MAIN OUTCOME MEASURE: The prevalence of dental fluorosis and clinical skeletal fluorosis, the fluoride concentrations in the drinking-water in study villages and in the urine of subjects. RESULTS: The study showed that in the villages where the drinking-water fluoride concentrations were higher than the government standard of 1.2 mg/l, but no fluoride-safe drinking-water supply scheme was provided (FNB areas), the prevalence rate and index of dental fluorosis in children, and prevalence rate of clinical skeletal fluorosis in adults were all significantly higher than those in the historical endemic fluorosis villages after the fluoride-safe drinking-water were provided (FSB areas). Additionally, the prevalence rate of dental fluorosis as well as clinical skeletal fluorosis, and the concentration of fluoride in urine were found increased with the increase of fluoride concentration in drinking-water, with significant positive correlations in the FNB areas. While, the prevalence rate of dental fluorosis and clinical skeletal fluorosis in different age groups and their degrees of prevalence were significantly lower in the FSB areas than those in the FNB areas. CONCLUSIONS: The provision of fluoride-safe drinking-water supply schemes had significant effects on the prevention and control of dental fluorosis and skeletal fluorosis. The study also indicated that the dental and skeletal fluorosis is still prevailing in the high-fluoride drinking-water areas in China.

Geographical distribution of drinking-water with high iodine level and association between high iodine level in drinking-water and goitre: a Chinese national investigation.

Excessive iodine intake can cause thyroid function disorders as can be caused by iodine deficiency. There are many people residing in areas with high iodine levels in drinking-water in China. The main aim of the present study was to map the geographical distribution of drinking-water with high iodine level in China and to determine the relationship between high iodine level in drinking-water and goitre prevalence. Iodine in drinking-water was measured in 1978 towns of eleven provinces in China, with a total of 28,857 water samples. We randomly selected children of 8-10 years old, examined the presence of goitre and measured their urinary iodine in 299 towns of nine provinces. Of the 1978 towns studied, 488 had iodine levels between 150 and 300 µg/l in drinking-water, and in 246 towns, the iodine level was >300 µg/l. These towns are mainly distributed along the original Yellow River flood areas, the second largest river in China. Of the 56 751 children examined, goitre prevalence was 6.3 % in the areas with drinking-water iodine levels of 150-300 µg/l and 11.0 % in the areas with drinking-water iodine >300 µg/l. Goitre prevalence increased with water and urinary iodine levels. For children with urinary iodine >1500 µg/l, goitre prevalence was 3.69 times higher than that for those with urinary iodine levels of 100-199 µg/l. The present study suggests that drinking-water with high iodine levels is distributed in eleven provinces of China. Goitre becomes more prevalent with the increase in iodine level in drinking-water. Therefore, it becomes important to prevent goitre through stopping the provision of iodised salt and providing normal drinking-water iodine through pipelines in these areas in China.

The relationships between low levels of urine fluoride on children's intelligence, dental fluorosis in endemic fluorosis areas in Hulunbuir, Inner Mongolia, China.

There has been public concern about children's intellectual performance at high levels of fluoride exposure, but few studies provide data directly to the question of whether low fluoride exposure levels less than 3.0 mg/L in drinking water adversely associated with children's intelligence. In this survey, we investigated the effects of low fluoride exposure on children's intelligence and dental fluorosis. 331 children aged from 7 to 14 were randomly recruited from four sites in Hulunbuir City, China. Intelligence was assessed using Combined Raven Test-The Rural in China while dental fluorosis was diagnosed with Dean's index. Mean value of fluoride in drinking water was 1.31±1.05 mg/L (range 0.24-2.84). Urine fluoride was inversely associated with IQ in the multiple linear regression model when children's age as a covariate variable was taken into account (P<0.0001). Each increase in 1 mg/L of urine fluoride associated with 0.59-point decrease in IQ (P=0.0226). Meanwhile, there was a dose-response relationship between urine fluoride and dental fluorosis (P<0.0001). In conclusion, our study suggested that low levels of fluoride exposure in drinking water had negative effects on children's intelligence and dental health and confirmed the dose-response relationships between urine fluoride and IQ scores as well as dental fluorosis.