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; 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 low-impact 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 micro-architecture, ex vivo osteogenic potential of BMPC, and BMPC expression of Runx-2, PPARγ 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/PPARγ 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/PPARγ ratio and up-regulation of RAGE. These diabetes-induced alterations can be totally or partially prevented by oral administration of metformin.
Fil: Tolosa, María José. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Chuguransky, Sara Rocío. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sedlinsky, Claudia. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Schurman, León. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina
Fil: McCarthy, Antonio Desmond. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina
Fil: Molinuevo, María Silvina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cortizo, Ana María. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Diabetes Mellitus
Metformin
Bone Microarchitecture
Bone Marrow Progenitor Cells
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/23357
Acceder
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network_name_str CONICET Digital (CONICET)
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 metformin.Tolosa, María JoséChuguransky, Sara RocíoSedlinsky, ClaudiaSchurman, LeónMcCarthy, Antonio DesmondMolinuevo, María SilvinaCortizo, Ana MaríaDiabetes MellitusMetforminBone MicroarchitectureBone Marrow Progenitor CellsAims Diabetes mellitus is associated with metabolic bone disease and increased low-impact 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 micro-architecture, ex vivo osteogenic potential of BMPC, and BMPC expression of Runx-2, PPARγ 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/PPARγ 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/PPARγ ratio and up-regulation of RAGE. These diabetes-induced alterations can be totally or partially prevented by oral administration of metformin.Fil: Tolosa, María José. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chuguransky, Sara Rocío. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sedlinsky, Claudia. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schurman, León. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; ArgentinaFil: McCarthy, Antonio Desmond. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; ArgentinaFil: Molinuevo, María Silvina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cortizo, Ana María. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier Ireland2013-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/23357Tolosa, María José; Chuguransky, Sara Rocío; Sedlinsky, Claudia; Schurman, León; McCarthy, Antonio Desmond; et al.; 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.; Elsevier Ireland; Diabetes Research and Clinical Practice; 101; 2; 6-2013; 177-1860168-8227CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0168822713002210info:eu-repo/semantics/altIdentifier/doi/10.1016/j.diabres.2013.05.016info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:03Zoai:ri.conicet.gov.ar:11336/23357instacron: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 09:57:03.487CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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
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
Chuguransky, Sara Rocío
Sedlinsky, Claudia
Schurman, León
McCarthy, Antonio Desmond
Molinuevo, María Silvina
Cortizo, Ana María
author Tolosa, María José
author_facet Tolosa, María José
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 Diabetes Mellitus
Metformin
Bone Microarchitecture
Bone Marrow Progenitor Cells
topic 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 low-impact 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 micro-architecture, ex vivo osteogenic potential of BMPC, and BMPC expression of Runx-2, PPARγ 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/PPARγ 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/PPARγ ratio and up-regulation of RAGE. These diabetes-induced alterations can be totally or partially prevented by oral administration of metformin.
Fil: Tolosa, María José. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Chuguransky, Sara Rocío. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sedlinsky, Claudia. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Schurman, León. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina
Fil: McCarthy, Antonio Desmond. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina
Fil: Molinuevo, María Silvina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cortizo, Ana María. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigación en Osteospatías y Metabolismo Mineral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Aims Diabetes mellitus is associated with metabolic bone disease and increased low-impact 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 micro-architecture, ex vivo osteogenic potential of BMPC, and BMPC expression of Runx-2, PPARγ 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/PPARγ 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/PPARγ 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
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/11336/23357
Tolosa, María José; Chuguransky, Sara Rocío; Sedlinsky, Claudia; Schurman, León; McCarthy, Antonio Desmond; et al.; 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.; Elsevier Ireland; Diabetes Research and Clinical Practice; 101; 2; 6-2013; 177-186
0168-8227
CONICET Digital
CONICET
url http://hdl.handle.net/11336/23357
identifier_str_mv Tolosa, María José; Chuguransky, Sara Rocío; Sedlinsky, Claudia; Schurman, León; McCarthy, Antonio Desmond; et al.; 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.; Elsevier Ireland; Diabetes Research and Clinical Practice; 101; 2; 6-2013; 177-186
0168-8227
CONICET Digital
CONICET
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language eng
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info:eu-repo/semantics/altIdentifier/doi/10.1016/j.diabres.2013.05.016
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
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dc.publisher.none.fl_str_mv Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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reponame_str CONICET Digital (CONICET)
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv 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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