Titanium and Zirconium Levels Are Associated with Changes in MicroRNAs Expression: Results from a Human Cross-Sectional Study on Obese Population.
OBJECTIVE
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.
Department of Biomedical, Surgical and Dental Sciences, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Via della Commenda 10, 20122, Milan, Italy.
Gianguido
http://orcid.org/0000-0001-6442-5591
G
Cossellu
EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
Valeria
V
Motta
EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
Laura
L
Dioni
EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
Laura
L
Angelici
Worker's Health Protection and Promotion Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Luisella
L
Vigna
Department of Biomedical, Surgical and Dental Sciences, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Via della Commenda 10, 20122, Milan, Italy.
Giampietro
G
Farronato
EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.|Worker's Health Protection and Promotion Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.|Epidemiology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Angela Cecilia
AC
Pesatori
EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
Valentina
V
Bollati
D003430:Cross-Sectional Studies; D006197:Hair / Q000737:chemistry; D006801:Humans; D013058:Mass Spectrometry; D035683:MicroRNAs / Q000032:analysis / Q000378:metabolism*; D015999:Multivariate Analysis; D009765:Obesity / Q000378:metabolism*; D014025:Titanium / Q000032:analysis / Q000378:metabolism*; D015040:Zirconium / Q000032:analysis / Q000378:metabolism*
C555159:MIRN142 microRNA, human; C550856:MIRN152 microRNA, human; C546818:MIRN193 microRNA, human; C573188:MIRN323 microRNA, human; C556347:MIRN335 microRNA, human; C547168:MIRN494 microRNA, human; D035683:MicroRNAs; D015040:Zirconium; D014025:Titanium