Fluoride Affects Calcium Homeostasis by Regulating Parathyroid Hormone, PTH-Related Peptide, and Calcium-Sensing Receptor Expression.

Parathyroid hormone (PTH), PTH-related peptide (PTHrP), and calcium-sensing receptor (CaSR) play important roles in maintaining calcium homeostasis. Here, we study the effect of fluoride on expression of PTH, PTHrP, and CaSR both in vitro and in vivo. MC3T3-E1 cells and Sprague-Dawley rats were treated with different concentrations of fluoride. Then, the free calcium ion concentration in cell culture supernatant and serum were measured by biochemical analyzer. The expression of PTH, PTHrP, and CaSR was analyzed by qRT-PCR and Western blot. We found that the low dose of fluoride increased ionized calcium (i[Ca(2+)]) and the high dose of fluoride decreased i[Ca(2+)] in cell culture supernatant. The low dose of fluoride inhibited the PTH and PTHrP expression in MC3T3-E1 cells. The high dose of fluoride improved the PTHrP expression in MC3T3-E1 cells. Interestingly, we found that NaF decreased serum i[Ca(2+)] in rats. Fluoride increased CaSR expression at both messenger RNA (mRNA) and protein levels in MC3T3-E1 cells and rats. The expression of PTHrP protein was inhibited by fluoride in rats fed regular diet and was increased by fluoride in rats fed low-calcium diet. Fluoride also increased the expression of PTH, NF-kappaB ligand (RANKL), and osteoprotegerin (OPG) in rats. The ratio of RANKL/OPG in rats fed low-calcium food in presence or absence of fluoride was significantly increased. These results indicated that fluoride might be able to affect calcium homeostasis by regulating PTH, PTHrP, and CaSR.

High-dose glucocorticoids induce decreases calcium in hypothalamus neurons via plasma membrane Ca(2+) pumps.

In our previous studies, we occasionally found that high-dose glucocorticoids (GC) induced decrease in [Ca(2+)](i) in hypothalamus neurons. In previous articles, modulation of Ca(2+) channels by GC has been shown to contribute to the elementary regulation of several neuronal functions. However, little is known about the regulation of the Ca efflux pathways that counterbalance the Ca(2+) influx in neurons caused by high-dose GC. In this study, we demonstrate that a high-dose of GC (10 M dexamethasone) caused a 20% decrease in [Ca(2+)](i) within 2 s in cultured hypothalamic neurons; furthermore, we show that an antagonist of the GC receptor blocks this action. To ascertain the temporal sequence of relevant calcium transport mechanisms we selectively blocked the main calcium transporters, including sodium/calcium exchanger (NCX), plasma membrane calcium pumps (PMCA), and P-type Ca(2+)-ATPases of the sarcoplasmic reticulum (SERCA). The GC-induced [Ca(2+)](i) decrease disappeared completely when PMCA was blocked, but not when NCX and SERCA were blocked. These results suggest that high-dose GC (10(-6) M) rapidly decreases [Ca(2+)](i) by activating PMCA but not NCX or SERCA.