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High extracellular calcium concentrations directly stimulate osteoclast apoptosis.

Abstract : 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.
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https://www.hal.inserm.fr/inserm-00746184
Contributor : Mickael Naassila <>
Submitted on : Saturday, October 27, 2012 - 7:50:19 PM
Last modification on : Saturday, August 15, 2020 - 8:26:03 PM

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Florence Lorget, S. Kamel, Romuald Mentaverri, A. Wattel, Mickaël Naassila, et al.. High extracellular calcium concentrations directly stimulate osteoclast apoptosis.. Biochemical and Biophysical Research Communications, Elsevier, 2000, 268 (3), pp.899-903. ⟨10.1006/bbrc.2000.2229⟩. ⟨inserm-00746184⟩

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