Analysis of the Role of Insulin Signaling in Bone Turnover Induced by Fluoride

Abstract

The role of insulin signaling on the mechanism underlying fluoride induced osteopathology was studied. We analyzed the expression of genes related with bone turnover and insulin signaling in rats treated by varying dose of fluoride with or without streptozotocin (STZ) in vivo. Furthermore, insulin receptor (InR) expression in MC3T3-E1 cells (pre-osteoblast cell line) was interfered with small interfering RNA (siRNA), and genes related with osteoblastic and osteoclastic differentiation were investigated in cells exposed to fluoride in vitro for 2 days. The in vivo study indicated the possible role of insulin in bone lesion induced by excessive amount of fluoride. Fluoride activated the InR and Insulin-like growth factor 1 (IGF1) signaling, which were involved in the mechanism underlying fluoride induced bone turnover. The TGFβ1 and Wnt10/β-catenin pathway took part in the mechanism of bone lesion induced by fluoride, and insulin probably modulated the TGFβ1 and β-catenin to exert action on bone turnover during the development of bone lesion. The in vitro study showed the concomitant decrease of OPG, osterix and OCN with inhibition of InR expression in osteoblast, and three genes still was low in cells co-treated with fluoride and InR siRNA, which suggested that fluoride probably stimulated the expression of OPG, osterix and OCN through InR signaling. In conclusion, insulin played the important role in bone lesion induced by excessive amount of fluoride through mediating InR receptor signaling, and IGF1 signaling probably exerted action on bone turnover caused by overdose of fluoride.

Fluoride Regulate Osteoblastic Transforming Growth Factor-β1 Signaling by Mediating Recycling of the Type I Receptor ALK5

“…However, excessive fluoride may result in skeletal fluorosis, a condition that patients display various bone lesions including osteosclerosis, osteoporosis and degenerative joint changes [ 4 , 5 ]. Although some investigators have reported many studies in fluoride and bone turnover [ 6 , 7 ], the pathogenic mechanism of the skeletal fluorosis was still unclear.…”

Systematic analysis of lncRNAs, miRNAs and mRNAs for the identification of biomarkers for osteoporosis in the mandible of ovariectomized mice

“…4A). Moreover, DEmiR-targeted DEGs were significantly involved in pathways, such as the peroxisome proliferator-activated receptor (PPAR) and insulin signaling pathways (26,27) (Fig. 4B).…”

Effects of fluoride on insulin signaling and bone metabolism in ovariectomized rats

“…Studies by Liu et al [37] performed in rats treated with fluoride suggest that osteoblasts are more sensitive to the toxic action of high dose of fluoride than osteoclasts. Indeed, the decreased bone area of the proximal tibial epiphysis observed in OVX-F group highlights the fact that fluoride treatment did not improve the quality of bone tissue.…”

“…The higher intensity of immunostaining for OCN in OVX-F animals compared to control observed in the present study corroborate the findings of Sun et al [32] who observed increased OCN expression in bone tissue of rats exposed to fluoride (20 mg/kg/day) for two months. Recent studies performed in cultured bone cells obtained from femurs of rats treated with fluoride suggest that this element can stimulate OCN production by activation of the insulin receptor signaling pathway in osteoblasts [37].…”