Synergistic Effect Of BMPs And MMPs On Bone Turnover In Fluorosis And Its Regulatory Mechanism

Endemic fluorosis severely impairs health of people, who live in countryside of china. It is the characteristic of fluorosis that potentiation of bone turnover results from abnormal accumulation of fluorine in bone tissue, and dental and skeletal fluorosis are the main phenotypes. In this study, four-week-old male wistar rats were used to reproduce the fluorosis models by drinking water containing 150mg/L sodium fluoride. In order to observe the progress of rat fluorosis, the occurrence of dental fluorosis was successively observed, the contents of serum fluorine and bone fluorine were examined and analyzed, X-ray photography and analysis of bone mineral density were used. The change of bone ultrasructure were observed by light microscope and routine transmission electron microscope, the contents of hormones, and cytokines in bone turnover were detected by radioimmunoassay and ELISA, the mRNA and protein expression of bone turnover related factors were analyzed by RT-PCR and western blot. According to these results, we analyze the effects of members of TGF-βsuperfamily and MMP/TIMP on bone turnover in fluorosis and the regulatory progress, and expect to determine the molecular mechanism of bone turnover in fluorosis and provide the new way for prevention and cure fluorosis. The conclusions are following. 1.The rat fluorosis model was reproducted by 150mg/L sodium fluoride in water. In rats treated with sodium fluoride, typical dental fluorosis appeared, contents of serum fluorine and bone fluorine increased, and ostosclerosis was observed in rat long bone. 2.Sodium fluoride markedly enhance the osteoblast activity, which manifested bone formation increased, and stimulated proliferation of osteoclast, but the osteoclast activity was impaired because the number of lysosome and the density of lysosome contents were decreased. 3. The increased PTH is involved in bone turnover in fluorosis and can be used as sensitive index. Sodium fluoride had no effect on the content of CT, but increased the serum BGP. 4.The level of IL-6 remained at high level in rats treated with sodium fluoride. Sodium fluoride had no effects on IL-1βand NO. 5.TGF-β1,BMP-2 and BMP-7 are involved in bone turnover in fluorosis, and their contents are most during earlier period of dosing fluorine.6.TIMP-1and MMP-13 are involved in bone turnover in fluorosis, but MMP-3 did not change in this process. 7.iNOS is involved in bone turnover in fluorosis.