Effect of metformin on bone marrow progenitor cell differentiation: In vivo and in vitro studies

Diabetes mellitus is associated with bone loss. Patients with type 2 diabetes are frequently treated with oral antidiabetic drugs such as sulfonylureas, biguanides, and thiazolidinediones. Rosiglitazone treatment has been shown to increase adipogenesis in bone marrow and to induce bone loss. In this...

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Autores principales: Molinuevo, María Silvina, Schurman, León, McCarthy, Antonio Desmond, Cortizo, Ana María, Tolosa, María José Anahí, Gangoiti, María Virginia, Arnol, Verónica, Sedlinsky, Claudia
Formato: Articulo
Lenguaje:Inglés
Publicado: 2010
Materias:
Ciencias Exactas
Bone marrow progenitor cells
Diabetes mellitus
Metformin
Osteoblastogenesis
Rosiglitazone
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/82465
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-82465
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
Bone marrow progenitor cells
Diabetes mellitus
Metformin
Osteoblastogenesis
Rosiglitazone
spellingShingle Ciencias Exactas
Bone marrow progenitor cells
Diabetes mellitus
Metformin
Osteoblastogenesis
Rosiglitazone
Molinuevo, María Silvina
Schurman, León
McCarthy, Antonio Desmond
Cortizo, Ana María
Tolosa, María José Anahí
Gangoiti, María Virginia
Arnol, Verónica
Sedlinsky, Claudia
Effect of metformin on bone marrow progenitor cell differentiation: In vivo and in vitro studies
topic_facet Ciencias Exactas
Bone marrow progenitor cells
Diabetes mellitus
Metformin
Osteoblastogenesis
Rosiglitazone
description Diabetes mellitus is associated with bone loss. Patients with type 2 diabetes are frequently treated with oral antidiabetic drugs such as sulfonylureas, biguanides, and thiazolidinediones. Rosiglitazone treatment has been shown to increase adipogenesis in bone marrow and to induce bone loss. In this study we evaluated the effect of in vivo and in vitro treatment with metformin on bone marrow progenitor cells (BMPCs), as well as the involvement of AMPK pathway in its effects. The in vitro effect of coincubation with metformin and rosiglitazone on the adipogenic differentiation of BMPCs also was studied. In addition, we evaluated the effect of in vivo metformin treatment on bone regeneration in a model of parietal lesions in nondiabetic and streptozotocin-induced diabetic rats. We found that metformin administration both in vivo and in vitro caused an increase in alkaline phosphatase activity, type I collagen synthesis, osteocalcin expression, and extracellular calcium deposition of BMPCs. Moreover, metformin significantly activated AMPK in undifferentiated BMPCs. In vivo, metformin administration enhanced the expression of osteoblast-specific transcription factor Runx2/Cbfa1 and activation of AMPK in a time-dependent manner. Metformin treatment also stimulated bone lesion regeneration in control and diabetic rats. In vitro, metformin partially inhibited the adipogenic actions of rosiglitazone on BMPCs. In conclusion, our results indicate that metformin causes an osteogenic effect both in vivo and in vitro, possibly mediated by Runx2/Cbfa1 and AMPK activation, suggesting a possible action of metformin in a shift toward the osteoblastic differentiation of BMPCs.
format Articulo
Articulo
author Molinuevo, María Silvina
Schurman, León
McCarthy, Antonio Desmond
Cortizo, Ana María
Tolosa, María José Anahí
Gangoiti, María Virginia
Arnol, Verónica
Sedlinsky, Claudia
author_facet Molinuevo, María Silvina
Schurman, León
McCarthy, Antonio Desmond
Cortizo, Ana María
Tolosa, María José Anahí
Gangoiti, María Virginia
Arnol, Verónica
Sedlinsky, Claudia
author_sort Molinuevo, María Silvina
title Effect of metformin on bone marrow progenitor cell differentiation: In vivo and in vitro studies
title_short Effect of metformin on bone marrow progenitor cell differentiation: In vivo and in vitro studies
title_full Effect of metformin on bone marrow progenitor cell differentiation: In vivo and in vitro studies
title_fullStr Effect of metformin on bone marrow progenitor cell differentiation: In vivo and in vitro studies
title_full_unstemmed Effect of metformin on bone marrow progenitor cell differentiation: In vivo and in vitro studies
title_sort effect of metformin on bone marrow progenitor cell differentiation: in vivo and in vitro studies
publishDate 2010
url http://sedici.unlp.edu.ar/handle/10915/82465
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