STRONTIUM RANELATE PREVENTS THE DELETERIOUS ACTION OF ADVANCED GLYCATION END PRODUCTS ON BONE MARROW PROGENITOR CELLS VIA ACTIVATION OF WNT PATHWAY

FERNANDEZ JM; MOLINUEVO MS; SCHURMAN L; SEDLINSKY C; MCCARTHY A

Congreso; IOF (international Osteoporosis Foundation Regionals Brazil´12 and 1º Latin America Osteoporosis Meeting; 2012

Aims/Objetivos/Objetivo: To evaluate the ability of strontium ranelate (SR) to prevent AGEs deleterious action on the osteoblastic differentiation of bone marrow progenitor cells (BMPC) in vitro. We also investigated the role of Wnt pathway and calcium channels in these possible actions of SR. Methods/Métodos/Métodos: BMPC were obtained from Sprague-Dawley young male rats by flushing their femoral diaphysary central cavity with DMEM. Cells were cultured in an incubator at 37ºC, 95% humidity and 5% CO2. After they reached confluence, the BMPC monolayer was trypsinized and cells were seedeed in adequate tissue culture plates. For osteoblastic differentiation, BMPC were further cultured in DMEM plus sodium b-glycerophosphate and ascorbic acid in the presence of 10μg/ml of either AGEs or non glycated serum abumin (BSA), with or without 0.1mM SR, for 15 days.BMPC differentiaton was evaluated assesing alkaline phosphatase activity (ALP) using p-nitrophenylphosphate as substrate; and collagen extracellular production by Sirius red stain. The phopshorylation of b-catenin, a key mediator of the Wnt pathway, was assessed by indirect inmunofluorescence. Results: We found that SR co-incubated with BSA, increases osteoblastic differentiation of BMPC by increasing both ALP activity (125% vs BSA, p