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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Authors: Bondar, Constanza María, Ormazabal, Maximiliano Emanuel, Crivaro, Andrea Natalia, Ferreyra Compagnucci, Malena María, Delpino, María Victoria, Rozenfeld, Paula Adriana, Mucci, Juan Marcos
Format: article
Status:Published version
Publication Date:2017
Country:Argentina
Institution:Consejo Nacional de Investigaciones Científicas y Técnicas
Repository:CONICET Digital (CONICET)
Language:English
OAI Identifier:oai:ri.conicet.gov.ar:11336/48768
Online Access:http://hdl.handle.net/11336/48768
Access Level:Open access
Keyword:Apoptotic Bodies
Bone
Gaucher Disease
Osteoclast
Osteocyte
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
id AR_097cb3ff1a31cdf420ebfeb77b7eef26
oai_identifier_str oai:ri.conicet.gov.ar:11336/48768
network_acronym_str AR
network_name_str Argentina
repository_id_str
dc.title.none.fl_str_mv Osteocyte alterations induce osteoclastogenesis in an in vitro model of gaucher disease
title Osteocyte alterations induce osteoclastogenesis in an in vitro model of gaucher disease
spellingShingle Osteocyte alterations induce osteoclastogenesis in an in vitro model of gaucher disease
Bondar, Constanza María
Apoptotic Bodies
Bone
Gaucher Disease
Osteoclast
Osteocyte
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
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
dc.creator.none.fl_str_mv Bondar, Constanza María
Ormazabal, Maximiliano Emanuel
Crivaro, Andrea Natalia
Ferreyra Compagnucci, Malena María
Delpino, María Victoria
Rozenfeld, Paula Adriana
Mucci, Juan Marcos
author Bondar, Constanza María
author_facet Bondar, Constanza María
Ormazabal, Maximiliano Emanuel
Crivaro, Andrea Natalia
Ferreyra Compagnucci, Malena María
Delpino, María Victoria
Rozenfeld, Paula Adriana
Mucci, Juan Marcos
author_role author
author2 Ormazabal, Maximiliano Emanuel
Crivaro, Andrea Natalia
Ferreyra Compagnucci, Malena María
Delpino, María Victoria
Rozenfeld, Paula Adriana
Mucci, Juan Marcos
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Apoptotic Bodies
Bone
Gaucher Disease
Osteoclast
Osteocyte
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
topic Apoptotic Bodies
Bone
Gaucher Disease
Osteoclast
Osteocyte
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
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.
publishDate 2017
dc.date.none.fl_str_mv 2017-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/48768
Bondar, Constanza María; Ormazabal, Maximiliano Emanuel; Crivaro, Andrea Natalia; Ferreyra Compagnucci, Malena María; Delpino, María Victoria; et al.; Osteocyte alterations induce osteoclastogenesis in an in vitro model of gaucher disease; MDPI AG; International Journal of Molecular Sciences; 18; 1; 1-2017; 1-15
1422-0067
CONICET Digital
CONICET
url http://hdl.handle.net/11336/48768
identifier_str_mv Bondar, Constanza María; Ormazabal, Maximiliano Emanuel; Crivaro, Andrea Natalia; Ferreyra Compagnucci, Malena María; Delpino, María Victoria; et al.; Osteocyte alterations induce osteoclastogenesis in an in vitro model of gaucher disease; MDPI AG; International Journal of Molecular Sciences; 18; 1; 1-2017; 1-15
1422-0067
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms18010112
info:eu-repo/semantics/altIdentifier/url/http://www.mdpi.com/1422-0067/18/1/112
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI AG
publisher.none.fl_str_mv MDPI AG
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1799195790593228800
spelling Osteocyte alterations induce osteoclastogenesis in an in vitro model of gaucher diseaseBondar, Constanza MaríaOrmazabal, Maximiliano EmanuelCrivaro, Andrea NataliaFerreyra Compagnucci, Malena MaríaDelpino, María VictoriaRozenfeld, Paula AdrianaMucci, Juan MarcosApoptotic BodiesBoneGaucher DiseaseOsteoclastOsteocytehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Gaucher 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.Fil: Bondar, Constanza María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Ormazabal, Maximiliano Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Crivaro, Andrea Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Ferreyra Compagnucci, Malena María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Delpino, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Rozenfeld, Paula Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Mucci, Juan Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaMDPI AG2017-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/48768Bondar, Constanza María; Ormazabal, Maximiliano Emanuel; Crivaro, Andrea Natalia; Ferreyra Compagnucci, Malena María; Delpino, María Victoria; et al.; Osteocyte alterations induce osteoclastogenesis in an in vitro model of gaucher disease; MDPI AG; International Journal of Molecular Sciences; 18; 1; 1-2017; 1-151422-0067CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/ijms18010112info:eu-repo/semantics/altIdentifier/url/http://www.mdpi.com/1422-0067/18/1/112info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T14:03:33Zoai:ri.conicet.gov.ar:11336/48768instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982024-05-08 14:03:33.813CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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