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

BMC Medical Genetics

Research Article

Emilie Laurier¹  Nathalie Amiable¹  Edith Gagnon¹  Jacques P. Brown²  Laëtitia Michou³ 

[1] CHU de Québec-Université Laval Research Centre, Quebec, QC, Canada;CHU de Québec-Université Laval Research Centre, Quebec, QC, Canada;Department of Medicine, Université Laval, Quebec, QC, Canada;CHU de Québec-Université Laval Research Centre, Quebec, QC, Canada;Department of Medicine, Université Laval, Quebec, QC, Canada;Department of Rheumatology, CHU de Québec-Université Laval, Quebec, QC, Canada;Rhumatologie- R4774, CHU de Québec-Université Laval, 2705 boulevard Laurier, G1V 4G2, Québec, Québec, Canada;

关键词: Paget’s disease of bone;    TM7SF4;    DC-STAMP protein;    Rare genetic variant;    Osteoclast;   

DOI  :  10.1186/s12881-017-0495-3

 received in 2017-08-03, accepted in 2017-11-09,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundDendritic 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.MethodsFifty 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.ResultsAfter 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.ConclusionsThis 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.

【 授权许可】

CC BY   
© The Author(s). 2017