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Effects of Sodium Fluoride Treatment In Vitro on Cell Proliferation, BMP-2 and BMP-3 Expression in Human Osteosarcoma MG-63 Cells

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Abstract

Chronic excessive fluoride intake may cause fluorosis, which chiefly manifests as bone damage (or skeletal fluorosis). However, the molecular mechanism of skeletal fluorosis has not been clarified up to the present. The objective of this study was to analyze the effects of fluoride treatment on two of bone morphogenetic protein family member (BMP-2 and BMP-3) expression and cell viability using human osteosarcoma MG-63 cells as a model. Sodium fluoride (NaF) had pro-proliferation effects at relatively moderate concentration, with 5 × 103 μmol/L having the best effects. At 2 × 104 μmol/L, NaF inhibits cell proliferation. BMP-2 and BMP-3 expression was significantly induced by 5 × 103 μmol/L NaF and, to lesser extent, by 2 × 104 μmol/L NaF. Correspondingly, mothers against decapentaplegic homolog 1 (Smad-1) increased at both doses of NaF, which indicated the BMP signaling pathway was activated. Notable increases in secreted alkaline phosphatase (ALP) were observed when cells were treated with 5 × 103 μmol/L NaF. A BMP specific inhibitor LDN193189 suppressed cell proliferation induced by 5 × 103 μmol/L NaF. Also, 2 × 104 μmol/L NaF induced apoptosis but likely through a mechanism unrelated to the BMP pathway. Collectively, data show that NaF had dose-dependent effects on cell proliferation as well as BMP-2 and BMP-3 expression in MG-63 cells and suggested that cell proliferation enhanced by NaF-induced BMP members may be a molecular mechanism underlying skeletal fluorosis.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (81360412) and Science and Technology Funds from the Department of Science and Technology of Guizhou Province (No. SY [2013] 3062 and J [2010] 2268).

Conflict of Interest

No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. The work described was original research that has not been published previously and not under consideration for publication elsewhere. The opinions expressed by the authors contributing to this journal do not necessarily reflect the opinions of the Guiyang Medical University with which the authors are affiliated.

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Authors and Affiliations

  1. Department of Environmental Hygiene, School of Public Health, Guiyang Medical University, 9 Beijing Road, Yunyan District, 550004, Guiyang, People’s Republic of China

    Yan Wei, Yanli Wu, Beibei Zeng & Hua Zhang

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  1. Yan Wei
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  2. Yanli Wu
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  3. Beibei Zeng
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  4. Hua Zhang
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Correspondence to Hua Zhang.

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Yan Wei, Associate Professor of Guiyang Medical University.

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Wei, Y., Wu, Y., Zeng, B. et al. Effects of Sodium Fluoride Treatment In Vitro on Cell Proliferation, BMP-2 and BMP-3 Expression in Human Osteosarcoma MG-63 Cells. Biol Trace Elem Res 162, 18–25 (2014). https://doi.org/10.1007/s12011-014-0148-8

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  • DOI: https://doi.org/10.1007/s12011-014-0148-8

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