Metformin prevents anti-osteogenic in vivo and ex vivo effects of rosiglitazone in rats
- Autores
- Sedlinsky, Claudia; Molinuevo, María Silvina; Cortizo, Ana María; Tolosa, María José; Felice, Juan Ignacio; Sbaraglini, María Laura; Schurman, León; McCarthy, Antonio Desmond
- Año de publicación
- 2011
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Long-term treatment with the insulin-sensitizer rosiglitazone reduces bone mass and increases fracture risk. We have recently shown that orally administered metformin stimulates bone reossification and increases the osteogenic potential of bone marrow progenitor cells (BMPC). In the present study we investigated the effect of a 2-week metformin and/or rosiglitazone treatment on bone repair, trabecular bone microarchitecture and BMPC osteogenic potential, in young male Sprague–Dawley rats. Compared to untreated controls, rosiglitazone monotherapy decreased bone regeneration, femoral metaphysis trabecular area, osteoblastic and osteocytic density, and TRAP activity associated with epiphyseal growth plates. It also decreased the ex vivo osteogenic commitment of BMPC, inducing an increase in PPARγ expression, and a decrease in Runx2/Cbfa1 expression, in AMP-kinase phosphorylation, and in osteoblastic differentiation and mineralization. After monotherapy with metformin, with the exception of PPARγ expression which was blunted, all of the above parameters were significantly increased (compared to untreated controls). Metformin/rosiglitazone co-treatment prevented all the in vivo and ex vivo anti-osteogenic effects of rosiglitazone monotherapy, with a reversion back to control levels of PPARγ, Runx2/Cbfa1 and AMP-kinase phosphorylation of BMPC. In vitro co-incubation of BMPC with metformin and compound C—an inhibitor of AMPK phosphorylation— abrogated the metformin-induced increase in type-1 collagen production, a marker of osteoblastic differentiation. In conclusion, in rodent models metformin not only induces direct osteogenic in vivo and ex vivo actions, butwhen it is administered orally in combination with rosiglitazone it can prevent several of the adverse effects that this thiazolidenedione shows on bone tissue.
- Materia
-
Ciencias Médicas
Bone marrow progenitor cells
Metformin
Rosiglitazone
Osteoblastogenesis
Trabecular bone microarchitecture
Bone reossification - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- http://creativecommons.org/licenses/by-nc-sa/4.0/
- Repositorio
- Institución
- Comisión de Investigaciones Científicas de la Provincia de Buenos Aires
- OAI Identificador
- oai:digital.cic.gba.gob.ar:11746/11952
Ver los metadatos del registro completo
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Metformin prevents anti-osteogenic in vivo and ex vivo effects of rosiglitazone in ratsSedlinsky, ClaudiaMolinuevo, María SilvinaCortizo, Ana MaríaTolosa, María JoséFelice, Juan IgnacioSbaraglini, María LauraSchurman, LeónMcCarthy, Antonio DesmondCiencias MédicasBone marrow progenitor cellsMetforminRosiglitazoneOsteoblastogenesisTrabecular bone microarchitectureBone reossificationLong-term treatment with the insulin-sensitizer rosiglitazone reduces bone mass and increases fracture risk. We have recently shown that orally administered metformin stimulates bone reossification and increases the osteogenic potential of bone marrow progenitor cells (BMPC). In the present study we investigated the effect of a 2-week metformin and/or rosiglitazone treatment on bone repair, trabecular bone microarchitecture and BMPC osteogenic potential, in young male Sprague–Dawley rats. Compared to untreated controls, rosiglitazone monotherapy decreased bone regeneration, femoral metaphysis trabecular area, osteoblastic and osteocytic density, and TRAP activity associated with epiphyseal growth plates. It also decreased the ex vivo osteogenic commitment of BMPC, inducing an increase in PPARγ expression, and a decrease in Runx2/Cbfa1 expression, in AMP-kinase phosphorylation, and in osteoblastic differentiation and mineralization. After monotherapy with metformin, with the exception of PPARγ expression which was blunted, all of the above parameters were significantly increased (compared to untreated controls). Metformin/rosiglitazone co-treatment prevented all the in vivo and ex vivo anti-osteogenic effects of rosiglitazone monotherapy, with a reversion back to control levels of PPARγ, Runx2/Cbfa1 and AMP-kinase phosphorylation of BMPC. In vitro co-incubation of BMPC with metformin and compound C—an inhibitor of AMPK phosphorylation— abrogated the metformin-induced increase in type-1 collagen production, a marker of osteoblastic differentiation. In conclusion, in rodent models metformin not only induces direct osteogenic in vivo and ex vivo actions, butwhen it is administered orally in combination with rosiglitazone it can prevent several of the adverse effects that this thiazolidenedione shows on bone tissue.2011info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://digital.cic.gba.gob.ar/handle/11746/11952enginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejphar.2011.07.033info:eu-repo/semantics/altIdentifier/issn/1879-0712info:eu-repo/semantics/altIdentifier/issn/0014-2999info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/reponame:CIC Digital (CICBA)instname:Comisión de Investigaciones Científicas de la Provincia de Buenos Airesinstacron:CICBA2025-09-04T09:43:22Zoai:digital.cic.gba.gob.ar:11746/11952Institucionalhttp://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 09:43:23.256CIC Digital (CICBA) - Comisión de Investigaciones Científicas de la Provincia de Buenos Airesfalse |
dc.title.none.fl_str_mv |
Metformin prevents anti-osteogenic in vivo and ex vivo effects of rosiglitazone in rats |
title |
Metformin prevents anti-osteogenic in vivo and ex vivo effects of rosiglitazone in rats |
spellingShingle |
Metformin prevents anti-osteogenic in vivo and ex vivo effects of rosiglitazone in rats Sedlinsky, Claudia Ciencias Médicas Bone marrow progenitor cells Metformin Rosiglitazone Osteoblastogenesis Trabecular bone microarchitecture Bone reossification |
title_short |
Metformin prevents anti-osteogenic in vivo and ex vivo effects of rosiglitazone in rats |
title_full |
Metformin prevents anti-osteogenic in vivo and ex vivo effects of rosiglitazone in rats |
title_fullStr |
Metformin prevents anti-osteogenic in vivo and ex vivo effects of rosiglitazone in rats |
title_full_unstemmed |
Metformin prevents anti-osteogenic in vivo and ex vivo effects of rosiglitazone in rats |
title_sort |
Metformin prevents anti-osteogenic in vivo and ex vivo effects of rosiglitazone in rats |
dc.creator.none.fl_str_mv |
Sedlinsky, Claudia Molinuevo, María Silvina Cortizo, Ana María Tolosa, María José Felice, Juan Ignacio Sbaraglini, María Laura Schurman, León McCarthy, Antonio Desmond |
author |
Sedlinsky, Claudia |
author_facet |
Sedlinsky, Claudia Molinuevo, María Silvina Cortizo, Ana María Tolosa, María José Felice, Juan Ignacio Sbaraglini, María Laura Schurman, León McCarthy, Antonio Desmond |
author_role |
author |
author2 |
Molinuevo, María Silvina Cortizo, Ana María Tolosa, María José Felice, Juan Ignacio Sbaraglini, María Laura Schurman, León McCarthy, Antonio Desmond |
author2_role |
author author author author author author author |
dc.subject.none.fl_str_mv |
Ciencias Médicas Bone marrow progenitor cells Metformin Rosiglitazone Osteoblastogenesis Trabecular bone microarchitecture Bone reossification |
topic |
Ciencias Médicas Bone marrow progenitor cells Metformin Rosiglitazone Osteoblastogenesis Trabecular bone microarchitecture Bone reossification |
dc.description.none.fl_txt_mv |
Long-term treatment with the insulin-sensitizer rosiglitazone reduces bone mass and increases fracture risk. We have recently shown that orally administered metformin stimulates bone reossification and increases the osteogenic potential of bone marrow progenitor cells (BMPC). In the present study we investigated the effect of a 2-week metformin and/or rosiglitazone treatment on bone repair, trabecular bone microarchitecture and BMPC osteogenic potential, in young male Sprague–Dawley rats. Compared to untreated controls, rosiglitazone monotherapy decreased bone regeneration, femoral metaphysis trabecular area, osteoblastic and osteocytic density, and TRAP activity associated with epiphyseal growth plates. It also decreased the ex vivo osteogenic commitment of BMPC, inducing an increase in PPARγ expression, and a decrease in Runx2/Cbfa1 expression, in AMP-kinase phosphorylation, and in osteoblastic differentiation and mineralization. After monotherapy with metformin, with the exception of PPARγ expression which was blunted, all of the above parameters were significantly increased (compared to untreated controls). Metformin/rosiglitazone co-treatment prevented all the in vivo and ex vivo anti-osteogenic effects of rosiglitazone monotherapy, with a reversion back to control levels of PPARγ, Runx2/Cbfa1 and AMP-kinase phosphorylation of BMPC. In vitro co-incubation of BMPC with metformin and compound C—an inhibitor of AMPK phosphorylation— abrogated the metformin-induced increase in type-1 collagen production, a marker of osteoblastic differentiation. In conclusion, in rodent models metformin not only induces direct osteogenic in vivo and ex vivo actions, butwhen it is administered orally in combination with rosiglitazone it can prevent several of the adverse effects that this thiazolidenedione shows on bone tissue. |
description |
Long-term treatment with the insulin-sensitizer rosiglitazone reduces bone mass and increases fracture risk. We have recently shown that orally administered metformin stimulates bone reossification and increases the osteogenic potential of bone marrow progenitor cells (BMPC). In the present study we investigated the effect of a 2-week metformin and/or rosiglitazone treatment on bone repair, trabecular bone microarchitecture and BMPC osteogenic potential, in young male Sprague–Dawley rats. Compared to untreated controls, rosiglitazone monotherapy decreased bone regeneration, femoral metaphysis trabecular area, osteoblastic and osteocytic density, and TRAP activity associated with epiphyseal growth plates. It also decreased the ex vivo osteogenic commitment of BMPC, inducing an increase in PPARγ expression, and a decrease in Runx2/Cbfa1 expression, in AMP-kinase phosphorylation, and in osteoblastic differentiation and mineralization. After monotherapy with metformin, with the exception of PPARγ expression which was blunted, all of the above parameters were significantly increased (compared to untreated controls). Metformin/rosiglitazone co-treatment prevented all the in vivo and ex vivo anti-osteogenic effects of rosiglitazone monotherapy, with a reversion back to control levels of PPARγ, Runx2/Cbfa1 and AMP-kinase phosphorylation of BMPC. In vitro co-incubation of BMPC with metformin and compound C—an inhibitor of AMPK phosphorylation— abrogated the metformin-induced increase in type-1 collagen production, a marker of osteoblastic differentiation. In conclusion, in rodent models metformin not only induces direct osteogenic in vivo and ex vivo actions, butwhen it is administered orally in combination with rosiglitazone it can prevent several of the adverse effects that this thiazolidenedione shows on bone tissue. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011 |
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 |
https://digital.cic.gba.gob.ar/handle/11746/11952 |
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https://digital.cic.gba.gob.ar/handle/11746/11952 |
dc.language.none.fl_str_mv |
eng |
language |
eng |
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info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejphar.2011.07.033 info:eu-repo/semantics/altIdentifier/issn/1879-0712 info:eu-repo/semantics/altIdentifier/issn/0014-2999 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ |
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openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by-nc-sa/4.0/ |
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CIC Digital (CICBA) - Comisión de Investigaciones Científicas de la Provincia de Buenos Aires |
repository.mail.fl_str_mv |
marisa.degiusti@sedici.unlp.edu.ar |
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