Bone Disease in Nephropathic Cystinosis: Beyond Renal Osteodystrophy

Autor: Cécile Acquaviva-Bourdain, Débora Claramunt-Taberner, Ségolène Gaillard, Irma Machuca-Gayet, Justine Bacchetta, Aurélia Bertholet-Thomas, Thomas Quinaux
Přispěvatelé: Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Référence des Maladies Rares du Calcium et du Phosphore (HFME - HCL), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), EPICIME-CIC 1407 de Lyon, Inserm, Service de Pharmacologie Clinique, CHU-Lyon, Service de Biochimie et Biologie Moléculaire Grand Est [HCL, Lyon] (Centre de Biologie et de Pathologie), Hospices Civils de Lyon (HCL), Machuca-Gayet, Irma
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Bone disease
[SDV]Life Sciences [q-bio]
Cystinosis
030232 urology & nephrology
mTor signaling
Review
Bioinformatics
Nephropathic cystinosis
lcsh:Chemistry
chemistry.chemical_compound
0302 clinical medicine
Bone cell
Renal osteodystrophy
lcsh:QH301-705.5
Spectroscopy
2. Zero hunger
Osteoblast
Renal osteodystrophy (ROD)
General Medicine
3. Good health
Computer Science Applications
[SDV] Life Sciences [q-bio]
Cystinosin
Osteoclast
Bone Remodeling
Bone Diseases
Cysteamine
Catalysis
Metabolic bone disease
Inorganic Chemistry
03 medical and health sciences
Nephropathic Cystinosis
medicine
CKD-MBD
Animals
Humans
Physical and Theoretical Chemistry
Bone
Molecular Biology
Chronic Kidney Disease-Mineral and Bone Disorder
business.industry
Organic Chemistry
medicine.disease
030104 developmental biology
Amino Acid Transport Systems
Neutral
lcsh:Biology (General)
lcsh:QD1-999
chemistry
Orphan disease
Mutation
business
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, MDPI, 2020, 21 (9), pp.3109. ⟨10.3390/ijms21093109⟩
International Journal of Molecular Sciences, 2020, 21 (9), pp.3109. ⟨10.3390/ijms21093109⟩
International Journal of Molecular Sciences, Vol 21, Iss 3109, p 3109 (2020)
ISSN: 1661-6596
1422-0067
DOI: 10.3390/ijms21093109⟩
Popis: International audience; Patients with chronic kidney disease (CKD) display significant mineral and bone disorders (CKD-MBD) that induce significant cardiovascular, growth and bone comorbidities. Nephropathic cystinosis is an inherited metabolic disorder caused by the lysosomal accumulation of cystine due to mutations in the CTNS gene encoding cystinosin, and leads to end-stage renal disease within the second decade. The cornerstone of management relies on cysteamine therapy to decrease lysosomal cystine accumulation in target organs. However, despite cysteamine therapy, patients display severe bone symptoms, and the concept of "cystinosis metabolic bone disease" is currently emerging. Even though its exact pathophysiology remains unclear, at least five distinct but complementary entities can explain bone impairment in addition to CKD-MBD: long-term consequences of renal Fanconi syndrome, malnutrition and copper deficiency, hormonal disturbances, myopathy, and intrinsic/iatrogenic bone defects. Direct effects of both CTNS mutation and cysteamine on osteoblasts and osteoclasts are described. Thus, the main objective of this manuscript is not only to provide a clinical update on bone disease in cystinosis, but also to summarize the current experimental evidence demonstrating a functional impairment of bone cells in this disease and to discuss new working hypotheses that deserve future research in the field.
Databáze: OpenAIRE
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