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

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 insul...

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Autores principales: Tolosa, María José Anahí, Chuguransky, Sara Rocío, Sedlinsky, Claudia, Schurman, León, McCarthy, Antonio Desmond, Molinuevo, María Silvina, Cortizo, Ana María
Formato: Articulo
Lenguaje:Inglés
Publicado: 2013
Materias:
Ciencias Exactas
Biología
Diabetes Mellitus
Metformin
Bone microarchitecture
Bone marrow progenitor cells
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/130692
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-130692
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Exactas
Biología
Diabetes Mellitus
Metformin
Bone microarchitecture
Bone marrow progenitor cells
spellingShingle Ciencias Exactas
Biología
Diabetes Mellitus
Metformin
Bone microarchitecture
Bone marrow progenitor cells
Tolosa, María José Anahí
Chuguransky, Sara Rocío
Sedlinsky, Claudia
Schurman, León
McCarthy, Antonio Desmond
Molinuevo, María Silvina
Cortizo, Ana María
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
topic_facet Ciencias Exactas
Biología
Diabetes Mellitus
Metformin
Bone microarchitecture
Bone marrow progenitor cells
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.
format Articulo
Articulo
author Tolosa, María José Anahí
Chuguransky, Sara Rocío
Sedlinsky, Claudia
Schurman, León
McCarthy, Antonio Desmond
Molinuevo, María Silvina
Cortizo, Ana María
author_facet Tolosa, María José Anahí
Chuguransky, Sara Rocío
Sedlinsky, Claudia
Schurman, León
McCarthy, Antonio Desmond
Molinuevo, María Silvina
Cortizo, Ana María
author_sort Tolosa, María José Anahí
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
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
publishDate 2013
url http://sedici.unlp.edu.ar/handle/10915/130692
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