Artículo
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
; Chuguransky, Sara Rocío
; Sedlinsky, Claudia; Schurman, León; McCarthy, Antonio Desmond; Molinuevo, María Silvina
; Cortizo, Ana María
Fecha de publicación:
06/2013
Editorial:
Elsevier Ireland
Revista:
Diabetes Research and Clinical Practice
ISSN:
0168-8227
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Resumen
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.
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Articulos(CCT - LA PLATA)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - LA PLATA
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - LA PLATA
Citación
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
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