%0 Journal Article %A Axelle Caudrillier %A Anne-Sophie Hurtel-Lemaire %A Alice Wattel %A Fabienne Cournarie %A Corinne Godin %A Laurent Petit %A Jean Pierre Petit %A Ernest Terwilliger %A Said Kamel %A Edward Meigs Brown %A Romuald Mentaverri %A Michel Brazier %T Strontium ranelate decreases RANKL-induced osteoclastic differentiation in vitro: involvement of the calcium sensing receptor. %D 2010 %R 10.1124/mol.109.063347 %J Molecular Pharmacology %P mol.109.063347 %X Strontium ranelate acts by increasing bone formation by osteoblast and decreasing bone resorption by osteoclasts. To further investigate the mechanism by which strontium ranelate inhibits bone resorption, the effects of varying concentrations of Sr2+o on osteoclastic differentiation were studied using RAW 264.7 cells and PBMC. We report that increasing concentrations of Sr2+o down-regulate osteoclastic differentiation and tartrate-resistant acid phosphatase (TRAP) activity, leading to inhibition of bone resorption (- 48% when PBMC were cultured for fourteen days in the presence of 2 mM Sr2+o). Using a dominant negative form of the CaR and a small interfering RNA approach, we provide evidences that the inhibition of osteoclast differentiation by Sr2+o is mediated by stimulation of the calcium-sensing receptor (CaR). Moreover, our results suggest that the effects of Sr2+o on osteoclasts are, at least in part, mediated by inhibition of the RANKL-induced nuclear translocation of NFkB and AP-1, in the early stages of osteoclastic differentiation. In conclusion, our data indicate that Sr2+ 1) directly inhibits the formation of mature osteoclasts through down-regulation of RANKL-induced osteoclast differentiation and 2) decreases osteoclast differentiation through the activation of the CaR.The American Society for Pharmacology and Experimental Therapeutics %U https://molpharm.aspetjournals.org/content/molpharm/early/2010/06/28/mol.109.063347.full.pdf