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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/193718
Ver los metadatos del registro completo
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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 Técnicas2025-09-03T09:58:04Zoai: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:34982025-09-03 09:58:04.391CONICET 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 |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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1842269499033649152 |
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13.13397 |