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Joint Bone Spine
Volume 86, n° 3
pages 373-380 (mai 2019)
Doi : 10.1016/j.jbspin.2018.12.007
accepted : 19 December 2018
Original Articles

Gene-environment interactions in Paget's disease of bone
 

Mohamed S. Numan a, Sonia Jean b, c, Mariam Dessay a, Edith Gagnon a, Nathalie Amiable a, Jacques P. Brown a, c, Laëtitia Michou a, c, d,
a CHU de Québec-Université Laval Research Centre, G1V 4G2, Québec, Canada 
b Institut national de santé publique du Québec, G1V 5B3, Québec, Canada 
c Department of Medicine, Université Laval, G1V 0A6, Québec, Canada 
d Department of Rheumatology, CHU de Québec-Université Laval, G1V 4G2, Québec, Canada 

Corresponding author at: Rhumatologie-R4774, CHU de Québec-Université Laval, 2705, boulevard Laurier, G1V 4G2, Québec, Canada.Rhumatologie-R4774CHU de Québec-Université Laval2705, boulevard LaurierQuébecG1V 4G2Canada
Abstract
Objectives

This study explored the role of outdoor and indoor air pollutants in Paget's disease of bone (PDB).

Methods

We performed a survey in 140 French-Canadian patients with PDB, including 39 carriers of p.Pro392Leu mutation (SQSTM1 gene) and 113 healthy not mutated controls. The survey covered outdoor air pollution near the residence and indoor air pollutants by focusing on heating fuels and exposure to tobacco smoke. In a subgroup of patients, urinary concentrations of 17 heavy metals and 11 polycyclic aromatic hydrocarbons were measured by mass spectrometry. In light of what we learned from the survey and urinary assays, we explored the in vitro effects of certain toxics on osteoclasts in PDB. We conducted in vitro monocytes differentiation from peripheral blood of more than 40 participants, whose osteoclasts were treated with or without the toxic. The morphology of osteoclasts, their bone resorption abilities, gene and protein expression levels, and cellular oxidative stress levels were assayed.

Results

An inhibitory effect of cigarette smoke condensate and heavy metals was observed on morphology and bone resorption activity of patients’ osteoclasts. SQSTM1 gene expression was upregulated in osteoclasts from patients with PDB versus healthy controls in presence of cadmium, and SQSTM1 protein expression was upregulated in presence of bismuth and tobacco smoke condensates, in particular in osteoclasts from carriers of the SQSTM1 mutation. Furthermore, high levels of oxidative stress in patients’ osteoclasts were observed.

Conclusions

Our in vitro experiments suggest an interaction between SQSTM1 gene and exposure to cadmium and tobacco smoke condensates.

The full text of this article is available in PDF format.

Keywords : Paget's disease of bone, SQSTM1 gene, Heavy metals, Cadmium, Osteoclast, Oxidative stress




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