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Artículo

Gaucher disease-associated alterations in mesenchymal stem cells reduce osteogenesis and favour adipogenesis processes with concomitant increased osteoclastogenesis

Crivaro, Andrea NataliaIcon ; Bondar, Constanza MaríaIcon ; Mucci, Juan MarcosIcon ; Ormazabal, Maximiliano EmanuelIcon ; Feldman, Ricardo A.; Delpino, María VictoriaIcon ; Rozenfeld, Paula AdrianaIcon
Fecha de publicación: 08/2020
Editorial: Academic Press Inc Elsevier Science
Revista: Molecular Genetics And Metabolism
ISSN: 1096-7192
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Inmunología

Resumen

Gaucher disease (GD) is caused by pathogenic mutations in GBA1, the gene that encodes the lysosomal enzyme β-glucocerebrosidase. Until now, treatments for GD cannot completely reverse bone problems. The aim of this work was to evaluate the potential of MSCs from GD patients (GD MSCs) to differentiate towards the osteoblast (GD Ob) and adipocyte (GD Ad) lineages, and their role in osteoclastogenesis. We observed that GD Ob exhibited reduced mineralization, collagen deposition and alkaline phosphatase activity (ALP), as well as decreased gene expression of RUNX2, COLA1 and ALP. We also evaluated the process of osteoclastogenesis and observed that conditioned media from GD MSCs supernatants induced an increase in the number of osteoclasts. In this model, osteoclastogenesis was induced by RANKL and IL-1β. Furthermore, results showed that in GD MSCs there was a promotion in NLRP3 and PPAR-γ gene expression. Adipogenic differentiation revealed that GD Ad had an increase in PPAR-γ and a reduced RUNX2 gene expression, promoting adipocyte differentiation. In conclusion, our results show that GD MSCs exhibited deficient GD Ob differentiation and increased adipogenesis. In addition, we show that GD MSCs promoted increased osteoclastogenesis through RANKL and IL-1β. These changes in GD MSCs are likely to contribute to skeletal imbalance observed in GD patients.
Palabras clave: ADIPOCYTE , GAUCHER , MSCS , OSTEOBLAST , OSTEOCLASTOGENESIS
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info:eu-repo/semantics/restrictedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/116875
URL: https://linkinghub.elsevier.com/retrieve/pii/S1096719220301426
DOI: http://dx.doi.org/10.1016/j.ymgme.2020.06.003
Colecciones
Articulos(IIFP)
Articulos de INST. DE ESTUDIOS INMUNOLOGICOS Y FISIOPATOLOGICOS
Articulos(INIGEM)
Articulos de INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Citación
Crivaro, Andrea Natalia; Bondar, Constanza María; Mucci, Juan Marcos; Ormazabal, Maximiliano Emanuel; Feldman, Ricardo A.; et al.; Gaucher disease-associated alterations in mesenchymal stem cells reduce osteogenesis and favour adipogenesis processes with concomitant increased osteoclastogenesis; Academic Press Inc Elsevier Science; Molecular Genetics And Metabolism; 130; 4; 8-2020; 274-282
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