Insulin-deficient diabetes-induced bone microarchitecture alterations are associated with a decrease in the osteogenic potential of bone marrow progenitor cells: Preventive effects...

Autores
Tolosa, María José Anahí; Chuguransky, Sara Rocío; Sedlinsky, Claudia; Schurman, León; McCarthy, Antonio Desmond; Molinuevo, María Silvina; Cortizo, Ana María
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Aims: Diabetes mellitus is associated with metabolic bone disease and increased lowimpact fractures. The insulin-sensitizer metformin possesses in vitro, in vivo and ex vivo osteogenic effects, although this has not been adequately studied in the context of diabetes. We evaluated the effect of insulin-deficient diabetes and/or metformin on bone microarchitecture, on osteogenic potential of bone marrow progenitor cells (BMPC) and possible mechanisms involved. Methods: Partially insulin-deficient diabetes was induced in rats by nicotinamide/streptozotocin-injection, with or without oral metformin treatment. Femoral metaphysis microarchitecture, ex vivo osteogenic potential of BMPC, and BMPC expression of Runx-2, PPARg and receptor for advanced glycation endproducts (RAGE) were investigated. Results: Histomorphometric analysis of diabetic femoral metaphysis demonstrated a slight decrease in trabecular area and a significant reduction in osteocyte density, growth plate height and TRAP (tartrate-resistant acid phosphatase) activity in the primary spongiosa. BMPC obtained from diabetic animals showed a reduction in Runx-2/PPARg ratio and in their osteogenic potential, and an increase in RAGE expression. Metformin treatment prevented the diabetes-induced alterations in bone micro-architecture and BMPC osteogenic potential. Conclusion: Partially insulin-deficient diabetes induces deleterious effects on long-bone micro-architecture that are associated with a decrease in BMPC osteogenic potential, which could be mediated by a decrease in their Runx-2/PPARg ratio and up-regulation of RAGE. These diabetes-induced alterations can be totally or partially prevented by oral administration of metformin.
Facultad de Ciencias Exactas
Laboratorio de Investigación en Osteopatías y Metabolismo Mineral
Materia
Ciencias Exactas
Biología
Diabetes Mellitus
Metformin
Bone microarchitecture
Bone marrow progenitor cells
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/130692
Acceder
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network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Insulin-deficient diabetes-induced bone microarchitecture alterations are associated with a decrease in the osteogenic potential of bone marrow progenitor cells: Preventive effects of metforminTolosa, María José AnahíChuguransky, Sara RocíoSedlinsky, ClaudiaSchurman, LeónMcCarthy, Antonio DesmondMolinuevo, María SilvinaCortizo, Ana MaríaCiencias ExactasBiologíaDiabetes MellitusMetforminBone microarchitectureBone marrow progenitor cellsAims: Diabetes mellitus is associated with metabolic bone disease and increased lowimpact fractures. The insulin-sensitizer metformin possesses in vitro, in vivo and ex vivo osteogenic effects, although this has not been adequately studied in the context of diabetes. We evaluated the effect of insulin-deficient diabetes and/or metformin on bone microarchitecture, on osteogenic potential of bone marrow progenitor cells (BMPC) and possible mechanisms involved. Methods: Partially insulin-deficient diabetes was induced in rats by nicotinamide/streptozotocin-injection, with or without oral metformin treatment. Femoral metaphysis microarchitecture, ex vivo osteogenic potential of BMPC, and BMPC expression of Runx-2, PPARg and receptor for advanced glycation endproducts (RAGE) were investigated. Results: Histomorphometric analysis of diabetic femoral metaphysis demonstrated a slight decrease in trabecular area and a significant reduction in osteocyte density, growth plate height and TRAP (tartrate-resistant acid phosphatase) activity in the primary spongiosa. BMPC obtained from diabetic animals showed a reduction in Runx-2/PPARg ratio and in their osteogenic potential, and an increase in RAGE expression. Metformin treatment prevented the diabetes-induced alterations in bone micro-architecture and BMPC osteogenic potential. Conclusion: Partially insulin-deficient diabetes induces deleterious effects on long-bone micro-architecture that are associated with a decrease in BMPC osteogenic potential, which could be mediated by a decrease in their Runx-2/PPARg ratio and up-regulation of RAGE. These diabetes-induced alterations can be totally or partially prevented by oral administration of metformin.Facultad de Ciencias ExactasLaboratorio de Investigación en Osteopatías y Metabolismo Mineral2013-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf177-186http://sedici.unlp.edu.ar/handle/10915/130692enginfo:eu-repo/semantics/altIdentifier/issn/1872-8227info:eu-repo/semantics/altIdentifier/issn/0168-8227info:eu-repo/semantics/altIdentifier/doi/10.1016/j.diabres.2013.05.016info:eu-repo/semantics/altIdentifier/pmid/23806481info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-03T11:04:23Zoai:sedici.unlp.edu.ar:10915/130692Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-03 11:04:23.598SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Insulin-deficient diabetes-induced bone microarchitecture alterations are associated with a decrease in the osteogenic potential of bone marrow progenitor cells: Preventive effects of metformin
title Insulin-deficient diabetes-induced bone microarchitecture alterations are associated with a decrease in the osteogenic potential of bone marrow progenitor cells: Preventive effects of metformin
spellingShingle Insulin-deficient diabetes-induced bone microarchitecture alterations are associated with a decrease in the osteogenic potential of bone marrow progenitor cells: Preventive effects of metformin
Tolosa, María José Anahí
Ciencias Exactas
Biología
Diabetes Mellitus
Metformin
Bone microarchitecture
Bone marrow progenitor cells
title_short Insulin-deficient diabetes-induced bone microarchitecture alterations are associated with a decrease in the osteogenic potential of bone marrow progenitor cells: Preventive effects of metformin
title_full Insulin-deficient diabetes-induced bone microarchitecture alterations are associated with a decrease in the osteogenic potential of bone marrow progenitor cells: Preventive effects of metformin
title_fullStr Insulin-deficient diabetes-induced bone microarchitecture alterations are associated with a decrease in the osteogenic potential of bone marrow progenitor cells: Preventive effects of metformin
title_full_unstemmed Insulin-deficient diabetes-induced bone microarchitecture alterations are associated with a decrease in the osteogenic potential of bone marrow progenitor cells: Preventive effects of metformin
title_sort Insulin-deficient diabetes-induced bone microarchitecture alterations are associated with a decrease in the osteogenic potential of bone marrow progenitor cells: Preventive effects of metformin
dc.creator.none.fl_str_mv Tolosa, María José Anahí
Chuguransky, Sara Rocío
Sedlinsky, Claudia
Schurman, León
McCarthy, Antonio Desmond
Molinuevo, María Silvina
Cortizo, Ana María
author Tolosa, María José Anahí
author_facet Tolosa, María José Anahí
Chuguransky, Sara Rocío
Sedlinsky, Claudia
Schurman, León
McCarthy, Antonio Desmond
Molinuevo, María Silvina
Cortizo, Ana María
author_role author
author2 Chuguransky, Sara Rocío
Sedlinsky, Claudia
Schurman, León
McCarthy, Antonio Desmond
Molinuevo, María Silvina
Cortizo, Ana María
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Exactas
Biología
Diabetes Mellitus
Metformin
Bone microarchitecture
Bone marrow progenitor cells
topic Ciencias Exactas
Biología
Diabetes Mellitus
Metformin
Bone microarchitecture
Bone marrow progenitor cells
dc.description.none.fl_txt_mv Aims: Diabetes mellitus is associated with metabolic bone disease and increased lowimpact fractures. The insulin-sensitizer metformin possesses in vitro, in vivo and ex vivo osteogenic effects, although this has not been adequately studied in the context of diabetes. We evaluated the effect of insulin-deficient diabetes and/or metformin on bone microarchitecture, on osteogenic potential of bone marrow progenitor cells (BMPC) and possible mechanisms involved. Methods: Partially insulin-deficient diabetes was induced in rats by nicotinamide/streptozotocin-injection, with or without oral metformin treatment. Femoral metaphysis microarchitecture, ex vivo osteogenic potential of BMPC, and BMPC expression of Runx-2, PPARg and receptor for advanced glycation endproducts (RAGE) were investigated. Results: Histomorphometric analysis of diabetic femoral metaphysis demonstrated a slight decrease in trabecular area and a significant reduction in osteocyte density, growth plate height and TRAP (tartrate-resistant acid phosphatase) activity in the primary spongiosa. BMPC obtained from diabetic animals showed a reduction in Runx-2/PPARg ratio and in their osteogenic potential, and an increase in RAGE expression. Metformin treatment prevented the diabetes-induced alterations in bone micro-architecture and BMPC osteogenic potential. Conclusion: Partially insulin-deficient diabetes induces deleterious effects on long-bone micro-architecture that are associated with a decrease in BMPC osteogenic potential, which could be mediated by a decrease in their Runx-2/PPARg ratio and up-regulation of RAGE. These diabetes-induced alterations can be totally or partially prevented by oral administration of metformin.
Facultad de Ciencias Exactas
Laboratorio de Investigación en Osteopatías y Metabolismo Mineral
description Aims: Diabetes mellitus is associated with metabolic bone disease and increased lowimpact fractures. The insulin-sensitizer metformin possesses in vitro, in vivo and ex vivo osteogenic effects, although this has not been adequately studied in the context of diabetes. We evaluated the effect of insulin-deficient diabetes and/or metformin on bone microarchitecture, on osteogenic potential of bone marrow progenitor cells (BMPC) and possible mechanisms involved. Methods: Partially insulin-deficient diabetes was induced in rats by nicotinamide/streptozotocin-injection, with or without oral metformin treatment. Femoral metaphysis microarchitecture, ex vivo osteogenic potential of BMPC, and BMPC expression of Runx-2, PPARg and receptor for advanced glycation endproducts (RAGE) were investigated. Results: Histomorphometric analysis of diabetic femoral metaphysis demonstrated a slight decrease in trabecular area and a significant reduction in osteocyte density, growth plate height and TRAP (tartrate-resistant acid phosphatase) activity in the primary spongiosa. BMPC obtained from diabetic animals showed a reduction in Runx-2/PPARg ratio and in their osteogenic potential, and an increase in RAGE expression. Metformin treatment prevented the diabetes-induced alterations in bone micro-architecture and BMPC osteogenic potential. Conclusion: Partially insulin-deficient diabetes induces deleterious effects on long-bone micro-architecture that are associated with a decrease in BMPC osteogenic potential, which could be mediated by a decrease in their Runx-2/PPARg ratio and up-regulation of RAGE. These diabetes-induced alterations can be totally or partially prevented by oral administration of metformin.
publishDate 2013
dc.date.none.fl_str_mv 2013-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
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://sedici.unlp.edu.ar/handle/10915/130692
url http://sedici.unlp.edu.ar/handle/10915/130692
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/1872-8227
info:eu-repo/semantics/altIdentifier/issn/0168-8227
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.diabres.2013.05.016
info:eu-repo/semantics/altIdentifier/pmid/23806481
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
177-186
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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