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Inhibition of Mdm2-p53 binding attenuates fluoride toxicity

Research Scholar

Huidan Deng, PhD candidate, Sichuan Agricultural University (China)
John D. Bartlett, faculty mentor


  • Hometown: Renshou, China
  • Degrees received: Bachelor of Science in veterinary medicine, Sichuan Agricultural University, China.

What is the issue or problem addresses in your research?

Fluoride is an effective caries prophylactic but excess fluoride intake can cause dental fluorosis resulting in hypomineralized, stained and brittle teeth. The number of children suffering from mild to severe dental fluorosis is increasing in the United States, India and China. However, the treatments for dental fluorosis are limited and the molecular pathways of fluoride toxicity remain unknown. Here, we characterized the fluoride-induced p53-MDM2 molecular pathway in ameloblasts-derived LS8 cells.

What methodology did you use in your research?

Ameloblasts-derived LS8 cells were treated with NaF (0-5 mM) for up to 24 h. Fluoride effects on p53, p21 and Mdm2 transcript expression were analyzed by quantitative real-time Polymerase chain reaction (PCR). Protein and posttranslational modification (acetylation, phosphorylation or ubiquitination) of p53, p21 and MDM2 were detected by western blot (WB) and immunocytochemistry. Activated-caspase-3 and γ-H2AX were detected by WB. Protein-protein interactions (MDM2-p53 and MDM2-p21) were analyzed by co-immunoprecipitation.

What are the purpose/rationale and implications of your research?

Public water fluoridation is beneficial for controlling tooth decay. However, fluoride over-exposure can cause dental fluorosis. Our long-term goal is to develop novel strategies that reduce dental fluorosis. To attain the objective, we have been investigating the molecular mechanisms of fluoride toxicity. Our results suggest MDM2-p53-p21 axis plays an important role to promote fluoride-induced toxicity. The MDM2-p53-p21 pathway may be a potential therapeutic target to mitigate dental fluorosis.