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

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Abstract

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[Ca2+]) and the high dose of fluoride decreased i[Ca2+] 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[Ca2+] 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.

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Acknowledgments

This work was supported by a grant for skeletal fluorosis research from the National Natural Science Foundation of China (81172608).

Conflict of Interest

All authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. The First Hospital, Norman Bethune of Jilin University, Changchun, 130041, People’s Republic of China

    Ying Wang

  2. Department of Rehabilitation Medicine of the Second Hospital, Norman Bethune of Jilin University, Changchun, 130041, People’s Republic of China

    Xiao-qin Duan & Huan Wang

  3. Institute of Endemic Disease, Jilin University, 1163 Xinmin Street, Changchun, 130021, People’s Republic of China

    Zhi-tao Zhao, Xiu-yun Zhang, Da-wei Liu, Guang-sheng Li & Ling Jing

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  1. Ying Wang
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Correspondence to Ling Jing.

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Wang, Y., Duan, Xq., Zhao, Zt. et al. Fluoride Affects Calcium Homeostasis by Regulating Parathyroid Hormone, PTH-Related Peptide, and Calcium-Sensing Receptor Expression. Biol Trace Elem Res 165, 159–166 (2015). https://doi.org/10.1007/s12011-015-0245-3

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