Titanium and Zirconium Levels Are Associated with Changes in MicroRNAs Expression: Results from a Human Cross-Sectional Study on Obese Population

PLoS One. 2016 Sep 9;11(9):e0161916. doi: 10.1371/journal.pone.0161916. eCollection 2016.

Abstract

Objectives: In this study on 90 individuals we aimed at evaluating the microRNAs (miRNAs) expression profile associated with personal levels of Titanium (Ti) and Zirconium (Zr) traced in hair samples. Ti and Zr materials are broadly used for dental implants but the biological reactions triggered by a long term presence of these materials in the oral cavity still need to be assessed. MiRNAs are mechanisms that need to be investigated as they play a fundamental role in the control of gene expression following external stimuli and contribute to a wide range of pathophysiological processes.

Methods: Using the TaqMan® Low-Density Array, we assessed the expression levels of 377 human miRNAs in peripheral blood of 90 subjects. Hair samples were analyzed for Ti and Zr content using Inductively Coupled Plasma-Mass Spectrometry. We performed multivariable regression analysis to investigate the effects of Ti and Zr exposure on miRNA expression levels. We used the Ingenuity Pathway Analysis (IPA) software to explore the functional role of the investigated miRNAs and the related target genes.

Results: Seven miRNAs (miR-99b, miR-142-5p, miR-152, miR-193a-5p, miR-323-3p, miR-335, miR-494) resulted specifically associated with Zr levels. The functional target analysis showed that miRNAs are involved in mechanisms such as inflammation, skeletal and connective tissue disorders.

Conclusions: Our data suggest that Zr is more bioactive than Ti and show that miRNAs are relevant molecular mechanisms sensitive to Zr exposure.

MeSH terms

  • Cross-Sectional Studies
  • Hair / chemistry
  • Humans
  • Mass Spectrometry
  • MicroRNAs / analysis
  • MicroRNAs / metabolism*
  • Multivariate Analysis
  • Obesity / metabolism*
  • Titanium / analysis
  • Titanium / metabolism*
  • Zirconium / analysis
  • Zirconium / metabolism*

Substances

  • MIRN142 microRNA, human
  • MIRN152 microRNA, human
  • MIRN193 microRNA, human
  • MIRN323 microRNA, human
  • MIRN335 microRNA, human
  • MIRN494 microRNA, human
  • MicroRNAs
  • Zirconium
  • Titanium

Grants and funding

This project received support from the EU Programme “Ideas” (ERC-2011-StG 282413 to Dr. V. Bollati).