RT Journal Article
SR Electronic
T1 Strontium Ranelate Decreases Receptor Activator of Nuclear Factor-κB Ligand-Induced Osteoclastic Differentiation In Vitro: Involvement of the Calcium-Sensing Receptor
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 569
OP 576
DO 10.1124/mol.109.063347
VO 78
IS 4
A1 Caudrillier, Axelle
A1 Hurtel-Lemaire, Anne-Sophie
A1 Wattel, Alice
A1 Cournarie, Fabienne
A1 Godin, Corinne
A1 Petit, Laurent
A1 Petit, Jean-Pierre
A1 Terwilliger, Ernest
A1 Kamel, Said
A1 Brown, Edward Meigs
A1 Mentaverri, Romuald
A1 Brazier, Michel
YR 2010
UL http://molpharm.aspetjournals.org/content/78/4/569.abstract
AB Strontium ranelate exerts both an anticatabolic and an anabolic effect on bone cells. To further investigate the mechanism by which strontium ranelate inhibits bone resorption, the effects of varying concentrations of Sro2+ on osteoclastic differentiation were studied using RAW 264.7 cells and peripheral blood monocytic cells (PBMCs). We report that increasing concentrations of Sro2+ down-regulate osteoclastic differentiation and tartrate-resistant acid phosphatase activity, leading to inhibition of bone resorption (−48% when PBMCs were cultured for 14 days in the presence of 2 mM Sro2+). Using a dominant-negative form of the calcium-sensing receptor (CaR) and a small interfering RNA approach, we provide evidences that the inhibition of osteoclast differentiation by Sro2+ is mediated by stimulation of the CaR. Moreover, our results suggest that the effects of Sro2+ on osteoclasts are, at least in part, mediated by inhibition of the receptor activator of nuclear factor-κB ligand (RANKL)-induced nuclear translocation of nuclear factor-κB and activator protein-1 in the early stages of osteoclastic differentiation. In conclusion, our data indicate that Sr2+ directly inhibits the formation of mature osteoclasts through down-regulation of RANKL-induced osteoclast differentiation and decreases osteoclast differentiation through the activation of the CaR.