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 ANAHÍ; CHUGURANSKY, SARA ROCÍO; SEDLINSKY CLAUDIA; SCHURMAN, LEON; MCCARTHY, ANTONIO DESMOND; MOLINUEVO, MARÍA SILVINA; CORTIZO, ANA MARÍA

DIABETES RESEARCH AND CLINICAL PRACTICE

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2013 p. 1 - 10

0168-8227

Aims: Diabetes mellitus is associated with metabolic bone disease and increased lowimpactfractures. The insulin-sensitizer metformin possesses in vitro, in vivo and ex vivoosteogenic 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 possiblemechanisms involved.Methods: Partially insulin-deficient diabetes was induced in rats by nicotinamide/strepto-zotocin-injection, with or without oral metformin treatment. Femoral metaphysis microarchitecture,ex vivo osteogenic potential of BMPC, and BMPC expression of Runx-2, PPARgand receptor for advanced glycation endproducts (RAGE) were investigated.Results: Histomorphometric analysis of diabetic femoral metaphysis demonstrated a slightdecrease in trabecular area and a significant reduction in osteocyte density, growth plateheight 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 theirosteogenic potential, and an increase in RAGE expression. Metformin treatment preventedthe diabetes-induced alterations in bone micro-architecture and BMPC osteogenic potential.Conclusion: Partially insulin-deficient diabetes induces deleterious effects on long-bonemicro-architecture that are associated with a decrease in BMPC osteogenic potential, whichcould 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 adminis-tration of metformin.