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Histone Deacetylation in the Promoter of p16 Is Involved in Fluoride-Induced Human Osteoblast Activation via the Inhibition of Sp1 Binding

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Abstract

Chronic fluorosis is a systemic condition which principally manifests as defects in the skeleton and teeth. Skeletal fluorosis is characterized by aberrant proliferation and activation of osteoblasts, however, the underlying mechanisms of osteoblast activation induced by fluoride are not fully understood. Therefore, we investigated the pathogenic mechanism of human primary osteoblast proliferation and activation in relation to histone acetylation of the promoter p16, a well-known cell cycle regulation-related gene. The results showed that sodium fluoride (NaF) induced deacetylation and decreased expression of the p16 gene via inhibition of specificity protein 1 (Sp1) binding to its response element, which accounts for NaF increasing cell viability and promoting proliferation in human primary osteoblasts. These results reveal the regulatory mechanism of histone acetylation of the p16 gene on osteoblast activation in skeletal fluorosis.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (No. 81260418) and the Nomarch Fund of Guizhou Province (No. [2011]54). The authors thank Donald L. Hill (University of Alabama at Birmingham, USA) for manuscript editing.

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Authors and Affiliations

  1. Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang, 550025, Guizhou, China

    Juan Ming, Shouli Wu, Tongzhao You, Xilan Wang, Chun Yu, Peng Luo, Aihua Zhang & Xueli Pan

  2. Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 550025, China

    Chun Yu, Peng Luo, Aihua Zhang & Xueli Pan

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  1. Juan Ming
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  2. Shouli Wu
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  4. Xilan Wang
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  5. Chun Yu
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  6. Peng Luo
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  7. Aihua Zhang
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  8. Xueli Pan
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Contributions

JM performed experiments, analyzed data, and drafted manuscript; SW, TY, XW, and CY performed experiments and contributed to the data acquisition; PL and AZ contributed toward study supervision; XP put forward the concept of the study, designed the study, and edited manuscript. All authors read and approved the final manuscript.

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Correspondence to Xueli Pan.

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The Institutional Ethics Committee for Scientific Research approved the study protocol, and a written consent was obtained from each participant of the study.

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The authors declare that they have no conflict of interest.

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Ming, J., Wu, S., You, T. et al. Histone Deacetylation in the Promoter of p16 Is Involved in Fluoride-Induced Human Osteoblast Activation via the Inhibition of Sp1 Binding. Biol Trace Elem Res 188, 373–383 (2019). https://doi.org/10.1007/s12011-018-1413-z

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