Role of fibroblast growth factor-23 in bone injury induced by fluoride in mice

Abstract

Objective To observe the effect of fluoride on fibroblast growth factor 23 (FGF23) in bone tissue of mice, and to explore the role of FGF23 in fluoride-induced bone injury. Methods Sixty-four Balb/c mice, half male and female, were divided into 4 groups based on body weight via the random number table method and 16 mice were in each group. The mice in control group, low fluoride group, middle fluoride group and high fluoride group were treated with 0, 25, 50, and 100 mg/L F- distilled water, respectively. After three months, the mice were put to death and the prevalence of dental fluorosis was calculated. The fluoride contents in spine were detected via the fluoride-ion selective electrode method, serum content of calcium and phosphorus were detected by micro enzyme labeled method. The levels of FGF23, parathyroid hormone (PTH) and 1,25 dihydroxy vitamin D3 [1,25(OH)2D3] in serum were measured by enzyme-linked immunosorbent assay. The FGF23 protein expression levels in bone tissue were determined by immunohistochemistry and Western blotting. Results The rates of dental fluorosis in low, medium and high fluoride groups were 75% (4/16), 100% (16/16) and 100% (16/16), respectively. Compared with control group [0(0/16)] the differences were statistically significant (P 0.05). The contents of phosphorus in the serum of the medium and the high fluoride groups [(2.46 ± 0.32), (2.48 ± 0.73) mmol/L] were lower than those in the control and the low fluoride groups [(2.89 ± 0.45), (3.25 ± 0.69) mmol/L, P < 0.05]. The serum PTH and 1,25 (OH)2D3 content increased first and then decreased. The expression of FGF23 in middle and high fluoride groups [(660.84 ± 64.18), (638.74 ± 121.23) ng/L] was up-regulated compared with that of control group [(613.53 ± 98.18) ng/L]. The expression of FGF23 protein in cortical bone increased gradually with the dose of fluoride. Western blotting results showed that the content of FGF23 protein in the bone tissue of mice was significantly increased in the low fluoride group (1.58 ± 0.46) and the middle fluoride group (1.40± 0.41) compared with that of control group (1.00 ± 0.41), the differences were statistically significant (P < 0.05). Conclusions The phosphorus, FGF23, PTH, and 1,25 (OH)2D3 levels in the serum and FGF23 protein levels in the bone tissue of fluorosis mice have changed. It may be suggested that FGF23 interacts with PTH and 1,25 (OH)2D3 to influence the level of calcium and phosphorus metabolism in the body and participate in the formation of skeletal fluorosis. Key words: Fluorosis; Fluoride on fibroblast growth factor 23; Parathyroid hormone; 1,25 dihydroxy vitamin D3; Phosphorus; Calcium