Bone marrow adipocytes alteration in an in vitro model of Gaucher Disease

Gaucher disease (GD) is caused by biallelic pathogenic variants in GBA1 gene that encodes the lysosomal enzyme glucocerebrosidase. Up to now, specific treatment for GD cannot completely reverse bone complications. Bone is composed of different cell types; including osteoblasts, osteocytes and osteoc...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Crivaro, Andrea Natalia, Mucci, Juan Marcos, Bondar, Constanza María, Ormazabal, Maximiliano Emanuel, Vaena, Emilio, Delpino, María Victoria
Formato: Articulo
Lenguaje:Inglés
Publicado: 2023
Materias:
Biología
Gaucher
MSCs
Adipocytes
Bone
Lipid droplets
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/160261
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-160261
record_format dspace
spelling I19-R120-10915-1602612023-11-16T20:06:29Z http://sedici.unlp.edu.ar/handle/10915/160261 Bone marrow adipocytes alteration in an in vitro model of Gaucher Disease Crivaro, Andrea Natalia Mucci, Juan Marcos Bondar, Constanza María Ormazabal, Maximiliano Emanuel Vaena, Emilio Delpino, María Victoria 2023 2023-11-16T18:12:33Z en Biología Gaucher MSCs Adipocytes Bone Lipid droplets Gaucher disease (GD) is caused by biallelic pathogenic variants in GBA1 gene that encodes the lysosomal enzyme glucocerebrosidase. Up to now, specific treatment for GD cannot completely reverse bone complications. Bone is composed of different cell types; including osteoblasts, osteocytes and osteoclasts. Osteoblasts are present on bone surfaces and are derived from local mesenchymal stem cells (MSCs). Depending on environment conditions, MSCs could differentiate into osteoblasts and adipocytes. Mature adipocytes-secreted adipokines and free fatty acids affect both osteoblasts and osteoclasts formation/activity and therefore mediate skeletal homeostasis. The aim of this study was to evaluate possible alterations in GD adipocyte (GD Ad) that could contribute to bone complications. MSCs were grown in adipogenic media in order to evaluate expression of differentiation markers as PPAR-γ. PPAR-γ was observed into the nucleus of GD Ad, indicating that these cells are properly stimulated. However, these cells accumulate lesser lipid droplets (LDs) than Control Ad. In order to study lipid droplet metabolism, we evaluated the lipolysis of these structures by the measurement of free glycerol in culture supernatant. Our results indicated that GD Ad had an alteration in this process, evidenced by an increase in glycerol release. We have also evaluated two enzymes involved in LDs synthesis: fatty acid synthase (FASN) and stearoylcoenzyme A desaturase 1 (SCD1). The transcription of these genes was decreased in GD Ad, suggesting a dysfunction in the synthesis of LDs. In conclusion, our results show an alteration in LDs metabolism of GD Ad, independent of adipocyte differentiation process. This alteration would be caused by an increase in lipolysis in early stages of differentiation and also by a reduction of lipid synthesis, which could contribute with the skeletal imbalance in GD. Instituto de Estudios Inmunológicos y Fisiopatológicos Articulo Articulo http://creativecommons.org/licenses/by-nc-nd/4.0/ Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) application/pdf
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
Gaucher
MSCs
Adipocytes
Bone
Lipid droplets
spellingShingle Biología
Gaucher
MSCs
Adipocytes
Bone
Lipid droplets
Crivaro, Andrea Natalia
Mucci, Juan Marcos
Bondar, Constanza María
Ormazabal, Maximiliano Emanuel
Vaena, Emilio
Delpino, María Victoria
Bone marrow adipocytes alteration in an in vitro model of Gaucher Disease
topic_facet Biología
Gaucher
MSCs
Adipocytes
Bone
Lipid droplets
description Gaucher disease (GD) is caused by biallelic pathogenic variants in GBA1 gene that encodes the lysosomal enzyme glucocerebrosidase. Up to now, specific treatment for GD cannot completely reverse bone complications. Bone is composed of different cell types; including osteoblasts, osteocytes and osteoclasts. Osteoblasts are present on bone surfaces and are derived from local mesenchymal stem cells (MSCs). Depending on environment conditions, MSCs could differentiate into osteoblasts and adipocytes. Mature adipocytes-secreted adipokines and free fatty acids affect both osteoblasts and osteoclasts formation/activity and therefore mediate skeletal homeostasis. The aim of this study was to evaluate possible alterations in GD adipocyte (GD Ad) that could contribute to bone complications. MSCs were grown in adipogenic media in order to evaluate expression of differentiation markers as PPAR-γ. PPAR-γ was observed into the nucleus of GD Ad, indicating that these cells are properly stimulated. However, these cells accumulate lesser lipid droplets (LDs) than Control Ad. In order to study lipid droplet metabolism, we evaluated the lipolysis of these structures by the measurement of free glycerol in culture supernatant. Our results indicated that GD Ad had an alteration in this process, evidenced by an increase in glycerol release. We have also evaluated two enzymes involved in LDs synthesis: fatty acid synthase (FASN) and stearoylcoenzyme A desaturase 1 (SCD1). The transcription of these genes was decreased in GD Ad, suggesting a dysfunction in the synthesis of LDs. In conclusion, our results show an alteration in LDs metabolism of GD Ad, independent of adipocyte differentiation process. This alteration would be caused by an increase in lipolysis in early stages of differentiation and also by a reduction of lipid synthesis, which could contribute with the skeletal imbalance in GD.
format Articulo
Articulo
author Crivaro, Andrea Natalia
Mucci, Juan Marcos
Bondar, Constanza María
Ormazabal, Maximiliano Emanuel
Vaena, Emilio
Delpino, María Victoria
author_facet Crivaro, Andrea Natalia
Mucci, Juan Marcos
Bondar, Constanza María
Ormazabal, Maximiliano Emanuel
Vaena, Emilio
Delpino, María Victoria
author_sort Crivaro, Andrea Natalia
title Bone marrow adipocytes alteration in an in vitro model of Gaucher Disease
title_short Bone marrow adipocytes alteration in an in vitro model of Gaucher Disease
title_full Bone marrow adipocytes alteration in an in vitro model of Gaucher Disease
title_fullStr Bone marrow adipocytes alteration in an in vitro model of Gaucher Disease
title_full_unstemmed Bone marrow adipocytes alteration in an in vitro model of Gaucher Disease
title_sort bone marrow adipocytes alteration in an in vitro model of gaucher disease
publishDate 2023
url http://sedici.unlp.edu.ar/handle/10915/160261
work_keys_str_mv AT crivaroandreanatalia bonemarrowadipocytesalterationinaninvitromodelofgaucherdisease
AT muccijuanmarcos bonemarrowadipocytesalterationinaninvitromodelofgaucherdisease
AT bondarconstanzamaria bonemarrowadipocytesalterationinaninvitromodelofgaucherdisease
AT ormazabalmaximilianoemanuel bonemarrowadipocytesalterationinaninvitromodelofgaucherdisease
AT vaenaemilio bonemarrowadipocytesalterationinaninvitromodelofgaucherdisease
AT delpinomariavictoria bonemarrowadipocytesalterationinaninvitromodelofgaucherdisease
_version_ 1807221877859418112

Ejemplares similares