Metformin prevents anti-osteogenic in vivo and ex vivo effects of rosiglitazone in rats

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...

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Autores: Sedlinsky, Claudia, Molinuevo, María Silvina, Cortizo, Ana María, Tolosa, María José, Felice, Juan Ignacio, Sbaraglini, María Laura, Schurman, León, McCarthy, Antonio Desmond
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2011
País:Argentina
Institución:Comisión de Investigaciones Científicas de la Provincia de Buenos Aires
Repositorio:CIC Digital (CICBA)
Idioma:inglés
OAI Identifier:oai:digital.cic.gba.gob.ar:11746/11952
Acceso en línea:https://digital.cic.gba.gob.ar/handle/11746/11952
Access Level:acceso abierto
Palabra clave:Ciencias Médicas
Bone marrow progenitor cells
Metformin
Rosiglitazone
Osteoblastogenesis
Trabecular bone microarchitecture
Bone reossification
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spelling 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:CICBA2024-05-10T10:39:05Zoai: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:94412024-05-10 10:39:05.69CIC 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
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
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info:eu-repo/semantics/publishedVersion
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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
url https://digital.cic.gba.gob.ar/handle/11746/11952
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 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/
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:CIC Digital (CICBA)
instname:Comisión de Investigaciones Científicas de la Provincia de Buenos Aires
instacron:CICBA
instname_str Comisión de Investigaciones Científicas de la Provincia de Buenos Aires
instacron_str CICBA
institution CICBA
reponame_str CIC Digital (CICBA)
collection CIC Digital (CICBA)
repository.name.fl_str_mv 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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