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

Autores
Molinuevo, M. Silvina; Schurman, Leon; McCarthy, Antonio Desmond; Cortizo, Ana María; Tolosa, María J.; Gangoiti, M. Virginia; Arnol, Veronica; Sedlinsky, Claudia
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión aceptada
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.
Materia
Ciencias Químicas
Bone Marrow Progenitor Cells
Metformin
Rosiglitazone
Osteoblastogenesis
Adipogénesis
Diabetes Mellitus
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
CIC Digital (CICBA)
Institución
Comisión de Investigaciones Científicas de la Provincia de Buenos Aires
OAI Identificador
oai:digital.cic.gba.gob.ar:11746/5047

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network_name_str CIC Digital (CICBA)
spelling Effect of metformin on bone marrow progenitor cell differentiation: in vivo and in vitro studiesMolinuevo, M. SilvinaSchurman, LeonMcCarthy, Antonio DesmondCortizo, Ana MaríaTolosa, María J.Gangoiti, M. VirginiaArnol, VeronicaSedlinsky, ClaudiaCiencias QuímicasBone Marrow Progenitor CellsMetforminRosiglitazoneOsteoblastogenesisAdipogénesisDiabetes MellitusDiabetes 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.2010-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://digital.cic.gba.gob.ar/handle/11746/5047enginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/reponame:CIC Digital (CICBA)instname:Comisión de Investigaciones Científicas de la Provincia de Buenos Airesinstacron:CICBA2025-09-04T09:42:55Zoai:digital.cic.gba.gob.ar:11746/5047Institucionalhttp://digital.cic.gba.gob.arOrganismo científico-tecnológicoNo correspondehttp://digital.cic.gba.gob.ar/oai/snrdmarisa.degiusti@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:94412025-09-04 09:42:55.596CIC Digital (CICBA) - Comisión de Investigaciones Científicas de la Provincia de Buenos Airesfalse
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, M. Silvina
Ciencias Químicas
Bone Marrow Progenitor Cells
Metformin
Rosiglitazone
Osteoblastogenesis
Adipogénesis
Diabetes Mellitus
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, M. Silvina
Schurman, Leon
McCarthy, Antonio Desmond
Cortizo, Ana María
Tolosa, María J.
Gangoiti, M. Virginia
Arnol, Veronica
Sedlinsky, Claudia
author Molinuevo, M. Silvina
author_facet Molinuevo, M. Silvina
Schurman, Leon
McCarthy, Antonio Desmond
Cortizo, Ana María
Tolosa, María J.
Gangoiti, M. Virginia
Arnol, Veronica
Sedlinsky, Claudia
author_role author
author2 Schurman, Leon
McCarthy, Antonio Desmond
Cortizo, Ana María
Tolosa, María J.
Gangoiti, M. Virginia
Arnol, Veronica
Sedlinsky, Claudia
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Químicas
Bone Marrow Progenitor Cells
Metformin
Rosiglitazone
Osteoblastogenesis
Adipogénesis
Diabetes Mellitus
topic Ciencias Químicas
Bone Marrow Progenitor Cells
Metformin
Rosiglitazone
Osteoblastogenesis
Adipogénesis
Diabetes Mellitus
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.
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
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info:eu-repo/semantics/acceptedVersion
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info:ar-repo/semantics/articulo
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://digital.cic.gba.gob.ar/handle/11746/5047
url https://digital.cic.gba.gob.ar/handle/11746/5047
dc.language.none.fl_str_mv eng
language eng
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http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:CIC Digital (CICBA)
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