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...
| Authors: | , , , , , , |
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| Format: | article |
| Status: | Published version |
| Publication Date: | 2013 |
| Country: | Argentina |
| Institution: | Universidad Nacional de La Plata |
| Repository: | SEDICI (UNLP) |
| Language: | English |
| OAI Identifier: | oai:sedici.unlp.edu.ar:10915/130692 |
| Online Access: | http://sedici.unlp.edu.ar/handle/10915/130692 |
| Access Level: | Open access |
| Keyword: | Ciencias Exactas Biología Diabetes Mellitus Metformin Bone microarchitecture Bone marrow progenitor cells |
| Summary: | 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. |
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