Abstract
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.
Keywords
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Article info
Publication history
Published online: June 26, 2013
Accepted:
May 30,
2013
Received in revised form:
May 21,
2013
Received:
March 14,
2013
Identification
Copyright
© 2013 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
