Osteocyte alterations induce osteoclastogenesis in an in vitro model of gaucher disease

Gaucher disease (GD) is caused by mutations in the glucosylceramidase β (GBA 1) gene that confer a deficient level of activity of glucocerebrosidase (GCase). This deficiency leads to the accumulation of the glycolipid glucocerebroside in the lysosomes of cells, mainly in the monocyte/macrophage line...

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Autores principales: Bondar, Constanza María, Ormazabal, Maximiliano, Crivaro, Andrea Natalia, Ferreyra Compagnucci, Malena, Delpino, María Victoria, Rozenfeld, Paula Adriana, Mucci, Juan Marcos
Formato: Articulo
Lenguaje:Inglés
Publicado: 2017
Materias:
Ciencias Exactas
Apoptotic bodies
Bone
Gaucher disease
Osteoclast
Osteocyte
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/87705
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-87705
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Exactas
Apoptotic bodies
Bone
Gaucher disease
Osteoclast
Osteocyte
spellingShingle Ciencias Exactas
Apoptotic bodies
Bone
Gaucher disease
Osteoclast
Osteocyte
Bondar, Constanza María
Ormazabal, Maximiliano
Crivaro, Andrea Natalia
Ferreyra Compagnucci, Malena
Delpino, María Victoria
Rozenfeld, Paula Adriana
Mucci, Juan Marcos
Osteocyte alterations induce osteoclastogenesis in an in vitro model of gaucher disease
topic_facet Ciencias Exactas
Apoptotic bodies
Bone
Gaucher disease
Osteoclast
Osteocyte
description Gaucher disease (GD) is caused by mutations in the glucosylceramidase β (GBA 1) gene that confer a deficient level of activity of glucocerebrosidase (GCase). This deficiency leads to the accumulation of the glycolipid glucocerebroside in the lysosomes of cells, mainly in the monocyte/macrophage lineage. Its mildest form is Type I GD, characterized by non-neuronopathic involvement. Bone compromise is the most disabling aspect of the Gaucher disease. However, the pathophysiological aspects of skeletal alterations are not yet fully understood. The bone tissue homeostasis is maintained by a balance between resorption of old bone by osteoclasts and new bone formation by osteoblasts. A central player in this balance is the osteocyte as it controls both processes. We studied the involvement of osteocytes in an in vitro chemical model of Gaucher disease. The osteocyte cell line MLO-Y4 was exposed to conduritol-β-epoxide (CBE), an inhibitor of GCase, for a period of 7, 14 and 21 days. Conditioned media from CBE-treated osteocytes was found to induce osteoclast differentiation. GCase inhibition caused alterations in Cx43 expression and distribution pattern and an increase in osteocyte apoptosis. Osteoclast differentiation involved osteocyte apoptotic bodies, receptor activator of nuclear factor κ-B ligand (RANKL) and soluble factors. Thus, our results indicate that osteocytes may have a role to play in the bone pathophysiology of GD.
format Articulo
Articulo
author Bondar, Constanza María
Ormazabal, Maximiliano
Crivaro, Andrea Natalia
Ferreyra Compagnucci, Malena
Delpino, María Victoria
Rozenfeld, Paula Adriana
Mucci, Juan Marcos
author_facet Bondar, Constanza María
Ormazabal, Maximiliano
Crivaro, Andrea Natalia
Ferreyra Compagnucci, Malena
Delpino, María Victoria
Rozenfeld, Paula Adriana
Mucci, Juan Marcos
author_sort Bondar, Constanza María
title Osteocyte alterations induce osteoclastogenesis in an in vitro model of gaucher disease
title_short Osteocyte alterations induce osteoclastogenesis in an in vitro model of gaucher disease
title_full Osteocyte alterations induce osteoclastogenesis in an in vitro model of gaucher disease
title_fullStr Osteocyte alterations induce osteoclastogenesis in an in vitro model of gaucher disease
title_full_unstemmed Osteocyte alterations induce osteoclastogenesis in an in vitro model of gaucher disease
title_sort osteocyte alterations induce osteoclastogenesis in an in vitro model of gaucher disease
publishDate 2017
url http://sedici.unlp.edu.ar/handle/10915/87705
work_keys_str_mv AT bondarconstanzamaria osteocytealterationsinduceosteoclastogenesisinaninvitromodelofgaucherdisease
AT ormazabalmaximiliano osteocytealterationsinduceosteoclastogenesisinaninvitromodelofgaucherdisease
AT crivaroandreanatalia osteocytealterationsinduceosteoclastogenesisinaninvitromodelofgaucherdisease
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bdutipo_str Repositorios
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