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Fluorosis Induces Endoplasmic Reticulum Stress and Apoptosis in Osteoblasts In Vivo

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Abstract

The present study investigated the effects of fluoride on endoplasmic reticulum (ER) stress (ERS) and osteoblast apoptosis in vivo. Forty-eight Wistar rats were randomly divided into four groups (12/group) and exposed to 0, 50, 100, and 150 mg/L of fluoride in drinking water for 8 weeks, respectively. Peripheral blood samples and bilateral femurs were used to monitor the progression of fluorosis in the animals. Hematoxylin and eosin (H&E) staining of the bone tissues was used to determine the severity of osteofluorosis. The expression of ERS chaperones (glucose-regulated protein 78 (GRP78), X-box binding protein l (XBP1), cysteine aspartate specific protease-12 (caspase-12), and growth arrest and DNA damage-inducible gene 153 (Gadd153/CHOP) was analyzed by immunohistochemistry staining, and osteoblast apoptosis was determined by TUNEL staining and flow cytometry. Accumulation of fluoride in bone was associated with the severity of osteofluorosis. The expression of GRP78, XBP1, caspase-12, and CHOP was increased in a dose-dependent manner. Fluoride-induced apoptosis in osteoblasts was also dose-dependent. High concentrations of fluoride induced ERS and osteoblast apoptosis in vivo. The increased expression of GRP78 and XBP1 increased the adaptation of osteoblasts to ERS to a certain extent. Caspase-12 and CHOP activation was associated with ERS and osteoblast apoptosis.

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Acknowledgments

This study was supported by a grant from the National Natural Science Foundation of China (No. 81072245) and the Natural Science Foundation of Liaoning Province (No. 20102278).

Conflicts of Interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Preventive Dentistry, School of Stomatology, China Medical University, ShenYang, China

    Lu Liu, Ying Zhang, Hefeng Gu, Kaiqiang Zhang & Lin Ma

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  1. Lu Liu
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  2. Ying Zhang
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Correspondence to Ying Zhang.

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Liu, L., Zhang, Y., Gu, H. et al. Fluorosis Induces Endoplasmic Reticulum Stress and Apoptosis in Osteoblasts In Vivo. Biol Trace Elem Res 164, 64–71 (2015). https://doi.org/10.1007/s12011-014-0192-4

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  • DOI: https://doi.org/10.1007/s12011-014-0192-4

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