PERSONAL DE APOYO
TOLOSA Maria Jose
artículos
Título:
Metformin prevents anti-osteogenic in vivo and ex vivo effects of Rosiglitazone in rats
Autor/es:
SEDLINSKY, CLAUDIA; MOLINUEVO, MARÍA SILVINA; CORTIZO, ANA MARÍA; TOLOSA, MARÍA JOSÉ ANAHÍ; FELICE, JUAN IGNACIO; SBARAGLINI, MARÍA LAURA; SCHURMAN, LEON; MCCARTHY, ANTONIO DESMOND
Revista:
EUROPEAN JOURNAL OF PHARMACOLOGY
Editorial:
ELSEVIER SCIENCE BV
Referencias:
Lugar: Amsterdam; Año: 2011 vol. 668 p. 477 - 485
ISSN:
0014-2999
Resumen:
Long-term
treatment with the insulin-sensitizer rosiglitazone reduces bone mass and
increases fracture risk. We have recently shown that orally administered
metformin stimulates bone reossification and increases the osteogenic potential
of bone marrow progenitor cells (BMPC). In the present study we investigated
the effect of a 2-week metformin and/or rosiglitazone treatment on bone repair,
trabecular bone microarchitecture and BMPC osteogenic potential, in young male
Sprague-Dawley rats. Compared to untreated controls, rosiglitazone monotherapy
decreased bone regeneration, femoral metaphysis trabecular area, osteoblastic
and osteocytic density, and TRAP activity associated with epiphyseal growth
plates. It also decreased the ex vivo osteogenic commitment of BMPC, inducing
an increase in PPARγ
expression, and a decrease in Runx2/Cbfa1 expression, in AMP-kinase
phosphorylation, and in osteoblastic differentiation and mineralization.
After
monotherapy with metformin, with the exception of PPARγ expression which was blunted, all of the above
parameters were significantly increased (compared to untreated controls).
Metformin/rosiglitazone co-treatment prevented all the in vivo and ex vivo
anti-osteogenic effects of rosiglitazone monotherapy, with a reversion back to
control levels of PPARγ,
Runx2/Cbfa1 and AMP-kinase phosphorylation of BMPC. In vitro co-incubation of
BMPC with metformin and compound C?an inhibitor of AMPK phosphorylation?
abrogated the metformin-induced increase in type-1 collagen production, a
marker of osteoblastic differentiation. In conclusion, in rodent models
metformin not only induces direct osteogenic in vivo and ex vivo actions,
butwhen it is administered orally in combination with rosiglitazone it can
prevent several of the adverse effects that this thiazolidenedione shows on
bone tissue.