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Response to Cysteamine in Osteoclasts Obtained from Patients with Nephropathic Cystinosis: A Genotype/Phenotype Correlation

Authors :
Thomas Quinaux
Aurélia Bertholet-Thomas
Aude Servais
Olivia Boyer
Isabelle Vrillon
Julien Hogan
Sandrine Lemoine
Ségolène Gaillard
Candide Alioli
Sophie Vasseur
Cécile Acquaviva
Olivier Peyruchaud
Irma Machuca-Gayet
Justine Bacchetta
Source :
Cells, Vol 10, Iss 9, p 2498 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

Bone complications of cystinosis have been recently described. The main objectives of this paper were to determine in vitro the impact of CTNS mutations and cysteamine therapy on human osteoclasts and to carry out a genotype-phenotype analysis related to osteoclastic differentiation. Human osteoclasts were differentiated from peripheral blood mononuclear cells (PBMCs) and were treated with increasing doses of cysteamine (0, 50, 200 µM) and then assessed for osteoclastic differentiation. Results are presented as median (min-max). A total of 17 patients (mainly pediatric) were included, at a median age of 14 (2–61) years, and a eGFR of 64 (23–149) mL/min/1.73 m2. Most patients (71%) were under conservative kidney management (CKM). The others were kidney transplant recipients. Three functional groups were distinguished for CTNS mutations: cystinosin variant with residual cystin efflux activity (RA, residual activity), inactive cystinosin variant (IP, inactive protein), and absent protein (AP). PBMCs from patients with residual cystinosin activity generate significantly less osteoclasts than those obtained from patients of the other groups. In all groups, cysteamine exerts an inhibitory effect on osteoclastic differentiation at high doses. This study highlights a link between genotype and osteoclastic differentiation, as well as a significant impact of cysteamine therapy on this process in humans.

Details

Language :
English
ISSN :
10092498 and 20734409
Volume :
10
Issue :
9
Database :
Directory of Open Access Journals
Journal :
Cells
Publication Type :
Academic Journal
Accession number :
edsdoj.6be2e1f48db7439d86dd22f90459c6fe
Document Type :
article
Full Text :
https://doi.org/10.3390/cells10092498