- 作者：Mar¨ªa Jos¨¦ Tolosa ; Sara Roc¨ªo Chuguransky ; Claudia Sedlinsky ; Le¨®n Schurman ; Antonio Desmond McCarthy ; Mar¨ªa Silvina Molinuevo ; Ana Mar¨ªa Cortizo
- 关键词：Diabetes mellitus ; Metformin ; Bone microarchitecture ; Bone marrow progenitor cells
- 刊名：Diabetes Research and Clinical Practice
- 出版年：2013
- 出版时间：August, 2013
- 年：2013
- 卷：101
- 期：2
- 页码：177-186
- 全文大小：1756 K
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, PPAR¦Ã 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/PPAR¦Ã 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/PPAR¦Ã ratio and up-regulation of RAGE. These diabetes-induced alterations can be totally or partially prevented by oral administration of metformin.