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; Gangoiti, Maria Virginia; Arnol, Veronica; 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.
Fil: Molinuevo, María Silvina. Universidad Nacional de La Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Schurman, León. Universidad Nacional de La Plata; Argentina
Fil: McCarthy, Antonio Desmond. Universidad Nacional de La Plata; Argentina
Fil: Cortizo, Ana María. Universidad Nacional de La Plata; Argentina
Fil: Tolosa, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata; Argentina
Fil: Gangoiti, Maria Virginia. Universidad Nacional de La Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Arnol, Veronica. Universidad Nacional de La Plata; Argentina
Fil: Sedlinsky, Claudia. Universidad Nacional de La Plata; Argentina
Materia
ADIPOGENESIS
BONE MARROW PROGENITOR CELLS
DIABETES MELLITUS
METFORMIN
OSTEOBLASTOGENESIS
ROSIGLITAZONE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/193718
Acceder
id CONICETDig_4c673b606ddb3bca4b532ac38b3ce68b
oai_identifier_str oai:ri.conicet.gov.ar:11336/193718
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Effect of metformin on bone marrow progenitor cell differentiation: In vivo and in vitro studiesMolinuevo, María SilvinaSchurman, LeónMcCarthy, Antonio DesmondCortizo, Ana MaríaTolosa, María JoséGangoiti, Maria VirginiaArnol, VeronicaSedlinsky, ClaudiaADIPOGENESISBONE MARROW PROGENITOR CELLSDIABETES MELLITUSMETFORMINOSTEOBLASTOGENESISROSIGLITAZONEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Diabetes 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.Fil: Molinuevo, María Silvina. Universidad Nacional de La Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Schurman, León. Universidad Nacional de La Plata; ArgentinaFil: McCarthy, Antonio Desmond. Universidad Nacional de La Plata; ArgentinaFil: Cortizo, Ana María. Universidad Nacional de La Plata; ArgentinaFil: Tolosa, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata; ArgentinaFil: Gangoiti, Maria Virginia. Universidad Nacional de La Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Arnol, Veronica. Universidad Nacional de La Plata; ArgentinaFil: Sedlinsky, Claudia. Universidad Nacional de La Plata; ArgentinaAmerican Society for Bone and Mineral Research2010-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/193718Molinuevo, María Silvina; Schurman, León; McCarthy, Antonio Desmond; Cortizo, Ana María; Tolosa, María José; et al.; Effect of metformin on bone marrow progenitor cell differentiation: In vivo and in vitro studies; American Society for Bone and Mineral Research; Journal of Bone and Mineral Research; 25; 2; 2-2010; 211-2210884-0431CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1359/jbmr.090732info:eu-repo/semantics/altIdentifier/url/https://asbmr.onlinelibrary.wiley.com/doi/full/10.1359/jbmr.090732info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:05:13Zoai:ri.conicet.gov.ar:11336/193718instacron: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:34982025-09-29 10:05:13.867CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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
ADIPOGENESIS
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
Gangoiti, Maria Virginia
Arnol, Veronica
Sedlinsky, Claudia
author Molinuevo, María Silvina
author_facet Molinuevo, María Silvina
Schurman, León
McCarthy, Antonio Desmond
Cortizo, Ana María
Tolosa, María José
Gangoiti, Maria Virginia
Arnol, Veronica
Sedlinsky, Claudia
author_role author
author2 Schurman, León
McCarthy, Antonio Desmond
Cortizo, Ana María
Tolosa, María José
Gangoiti, Maria Virginia
Arnol, Veronica
Sedlinsky, Claudia
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ADIPOGENESIS
BONE MARROW PROGENITOR CELLS
DIABETES MELLITUS
METFORMIN
OSTEOBLASTOGENESIS
ROSIGLITAZONE
topic ADIPOGENESIS
BONE MARROW PROGENITOR CELLS
DIABETES MELLITUS
METFORMIN
OSTEOBLASTOGENESIS
ROSIGLITAZONE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
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.
Fil: Molinuevo, María Silvina. Universidad Nacional de La Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Schurman, León. Universidad Nacional de La Plata; Argentina
Fil: McCarthy, Antonio Desmond. Universidad Nacional de La Plata; Argentina
Fil: Cortizo, Ana María. Universidad Nacional de La Plata; Argentina
Fil: Tolosa, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata; Argentina
Fil: Gangoiti, Maria Virginia. Universidad Nacional de La Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Arnol, Veronica. Universidad Nacional de La Plata; Argentina
Fil: Sedlinsky, Claudia. Universidad Nacional de La Plata; Argentina
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 2010-02
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/11336/193718
Molinuevo, María Silvina; Schurman, León; McCarthy, Antonio Desmond; Cortizo, Ana María; Tolosa, María José; et al.; Effect of metformin on bone marrow progenitor cell differentiation: In vivo and in vitro studies; American Society for Bone and Mineral Research; Journal of Bone and Mineral Research; 25; 2; 2-2010; 211-221
0884-0431
CONICET Digital
CONICET
url http://hdl.handle.net/11336/193718
identifier_str_mv Molinuevo, María Silvina; Schurman, León; McCarthy, Antonio Desmond; Cortizo, Ana María; Tolosa, María José; et al.; Effect of metformin on bone marrow progenitor cell differentiation: In vivo and in vitro studies; American Society for Bone and Mineral Research; Journal of Bone and Mineral Research; 25; 2; 2-2010; 211-221
0884-0431
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1359/jbmr.090732
info:eu-repo/semantics/altIdentifier/url/https://asbmr.onlinelibrary.wiley.com/doi/full/10.1359/jbmr.090732
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
dc.publisher.none.fl_str_mv American Society for Bone and Mineral Research
publisher.none.fl_str_mv American Society for Bone and Mineral Research
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
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
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score 13.070432

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