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

Autores
Molinuevo, María Silvina; Schurman, León; McCarthy, Antonio Desmond; Cortizo, Ana María; Tolosa, María José Anahí; Gangoiti, María Virginia; Arnol, Verónica; Sedlinsky, Claudia
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Facultad de Ciencias Exactas
Materia
Ciencias Exactas
Bone marrow progenitor cells
Diabetes mellitus
Metformin
Osteoblastogenesis
Rosiglitazone
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/82465

id SEDICI_b7aec1b1813824b3e78465b1070227c2
oai_identifier_str oai:sedici.unlp.edu.ar:10915/82465
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Effect of metformin on bone marrow progenitor cell differentiation: In vivo and in vitro studiesMolinuevo, María SilvinaSchurman, LeónMcCarthy, Antonio DesmondCortizo, Ana MaríaTolosa, María José AnahíGangoiti, María VirginiaArnol, VerónicaSedlinsky, ClaudiaCiencias ExactasBone marrow progenitor cellsDiabetes mellitusMetforminOsteoblastogenesisRosiglitazoneDiabetes 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.Facultad de Ciencias Exactas2010info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf211-221http://sedici.unlp.edu.ar/handle/10915/82465enginfo:eu-repo/semantics/altIdentifier/issn/0884-0431info:eu-repo/semantics/altIdentifier/doi/10.1359/jbmr.090732info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-03T10:47:47Zoai:sedici.unlp.edu.ar:10915/82465Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-03 10:47:47.368SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Effect of metformin on bone marrow progenitor cell differentiation: In vivo and in vitro studies
title Effect of metformin on bone marrow progenitor cell differentiation: In vivo and in vitro studies
spellingShingle Effect of metformin on bone marrow progenitor cell differentiation: In vivo and in vitro studies
Molinuevo, María Silvina
Ciencias Exactas
Bone marrow progenitor cells
Diabetes mellitus
Metformin
Osteoblastogenesis
Rosiglitazone
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
dc.creator.none.fl_str_mv Molinuevo, María Silvina
Schurman, León
McCarthy, Antonio Desmond
Cortizo, Ana María
Tolosa, María José Anahí
Gangoiti, María Virginia
Arnol, Verónica
Sedlinsky, Claudia
author Molinuevo, María Silvina
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_role author
author2 Schurman, León
McCarthy, Antonio Desmond
Cortizo, Ana María
Tolosa, María José Anahí
Gangoiti, María Virginia
Arnol, Verónica
Sedlinsky, Claudia
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Exactas
Bone marrow progenitor cells
Diabetes mellitus
Metformin
Osteoblastogenesis
Rosiglitazone
topic Ciencias Exactas
Bone marrow progenitor cells
Diabetes mellitus
Metformin
Osteoblastogenesis
Rosiglitazone
dc.description.none.fl_txt_mv 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.
Facultad de Ciencias Exactas
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.
publishDate 2010
dc.date.none.fl_str_mv 2010
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
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://sedici.unlp.edu.ar/handle/10915/82465
url http://sedici.unlp.edu.ar/handle/10915/82465
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/0884-0431
info:eu-repo/semantics/altIdentifier/doi/10.1359/jbmr.090732
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
211-221
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
_version_ 1842260351056347136
score 13.13397