%0 Journal Article %T High extracellular calcium concentrations directly stimulate osteoclast apoptosis. %+ Laboratoires de Pharmacie Clinique et de Physiologie %+ Laboratoire Innothéra %A Lorget, Florence %A Kamel, Saïd %A Mentaverri, Romuald %A Wattel, A. %A Naassila, Mickaël %A Maamer, M. %A Brazier, Michel %< avec comité de lecture %@ 0006-291X %J Biochemical and Biophysical Research Communications %I Elsevier %V 268 %N 3 %P 899-903 %8 2000-02-24 %D 2000 %R 10.1006/bbrc.2000.2229 %M 10679302 %Z Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]Journal articles %X Although the inhibitory effects of high extracellular calcium concentrations ([Ca](e)) on osteoclastic bone resorption have been known for several years, the exact mechanism remains poorly understood. The present study was performed to investigate the possible effect of [Ca](e) on osteoclast apoptosis. Using highly purified rabbit osteoclasts, we have shown that calcium directly promotes apoptosis in a dose-dependent manner which correlates with the dose range of calcium for the inhibition of bone resorption. A time-course experiment of apoptotic changes of osteoclasts cultured in presence of 1.8 or 20 mM calcium showed a significant difference after as early as 8 h of culture. After 72 h of culture, we observed that 80% of the cells cultured in the presence of 20 mM calcium displayed the typical features of apoptosis compared to only 20% in the medium containing 1.8 mM calcium. Calcium channel blockers and ryanodine abrogated the effects of [Ca](e) on apoptosis while neomycin, a calcium-sensing receptor agonist, did not alter cell viability. Taken together, these results suggest that calcium influx is involved in calcium-induced osteoclast apoptosis. Our results are consistent with the concept that in the presence of high [Ca](e) generated during bone demineralization, osteoclasts are subjected to negative-feedback regulation due, at least in part, to the induction of apoptosis. %G English %L inserm-00746184 %U https://inserm.hal.science/inserm-00746184 %~ INSERM %~ UNIV-PICARDIE %~ U-PICARDIE