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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2017

Open Access 01-12-2017 | Research article

Effect of a rare genetic variant of TM7SF4 gene on osteoclasts of patients with Paget’s disease of bone

Authors: Emilie Laurier, Nathalie Amiable, Edith Gagnon, Jacques P. Brown, Laëtitia Michou

Published in: BMC Medical Genetics | Issue 1/2017

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Abstract

Background

Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) is involved in osteoclastogenesis with a key role in mononucleated osteoclasts fusion. We reported in patients with Paget’s disease of bone (PDB) a rare variant (rs62620995) in the TM7SF4 gene, encoding for DC-STAMP, which changes a highly conserved amino acid, possibly damaging according to in silico predictions. This study aimed at determining the functional effects of this variant on osteoclast phenotype in PDB.

Methods

Fifty ml of peripheral blood were collected in pagetic patients carrier of this variant (n = 4) or not (n = 4) and healthy controls (n = 4). Monocytes were collected after Ficoll gradient and cultured in a medium containing RANKL (40 ng/ml) and hMCSF (25 ng/ml). At the end of the differentiation period, we assessed the osteoclast morphology and bone resorption abilities. We quantified gene expression of SQSTM1, DC-STAMP, OS9, CREB3, LAMP1, OC-STAMP, and NFATC1 genes from cell lysates. Proteins encoded by these genes were investigated by Western Blot. Statistical analyses relied on ANOVA followed by Tukey post-tests.

Results

After 21 days of differentiation, the mean number of nuclei per multinucleated cell was significantly higher in pagetic patients carrier of the variant than in healthy controls. Bone resorption abilities were not modified by the variant. qPCR and Western Blot analyses did not provide any differences, but DC-STAMP expression was higher in patients carrier of the variant than in patients non carrier.

Conclusions

This TM7SF4 rare variant may have an impact on osteoclast morphology and on DC-STAMP expression during osteoclastogenesis. Further analyses are required to understand the role of this variant during osteoclastogenesis in PDB.
Appendix
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Metadata
Title
Effect of a rare genetic variant of TM7SF4 gene on osteoclasts of patients with Paget’s disease of bone
Authors
Emilie Laurier
Nathalie Amiable
Edith Gagnon
Jacques P. Brown
Laëtitia Michou
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2017
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-017-0495-3

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