High extracellular calcium concentrations directly stimulate osteoclast apoptosis.
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.
Lorget
F
F
Laboratoires de Pharmacie Clinique et de Physiologie, Faculté de Pharmacie, 1 rue des Louvels, Amiens, F-80037, France. florence.lorget@sa.u-picardie.fr
Kamel
S
S
Mentaverri
R
R
Wattel
A
A
Naassila
M
M
Maamer
M
M
Brazier
M
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001862:Bone Resorption / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits
D002118:Calcium