Lorget F, Kamel S, Mentaverri R, Wattel A, Naassila M, Maamer M, Brazier M
Laboratoires de Pharmacie Clinique et de Physiologie, Faculté de Pharmacie, 1 rue des Louvels, Amiens, F-80037, France.
Biochem Biophys Res Commun. 2000 Feb 24;268(3):899-903. doi: 10.1006/bbrc.2000.2229.
Although the inhibitory effects of high extracellular calcium concentrations (Ca) 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 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 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 generated during bone demineralization, osteoclasts are subjected to negative-feedback regulation due, at least in part, to the induction of apoptosis.
尽管细胞外高钙浓度（Ca）对破骨细胞骨吸收的抑制作用已为人所知数年，但确切机制仍知之甚少。本研究旨在探讨Ca对破骨细胞凋亡的可能影响。使用高度纯化的兔破骨细胞，我们发现钙以剂量依赖的方式直接促进凋亡，这与抑制骨吸收的钙剂量范围相关。在1.8或20 mM钙存在下培养破骨细胞的凋亡变化的时间进程实验显示，早在培养8小时后就有显著差异。培养72小时后，我们观察到，在20 mM钙存在下培养的细胞中，80%表现出典型的凋亡特征，而在含有1.8 mM钙的培养基中只有20%。钙通道阻滞剂和ryanodine消除了Ca对凋亡的影响，而钙敏感受体激动剂新霉素并未改变细胞活力。综上所述，这些结果表明钙内流参与了钙诱导的破骨细胞凋亡。我们的结果与以下概念一致，即在骨脱矿过程中产生的高Ca存在下，破骨细胞至少部分地由于凋亡的诱导而受到负反馈调节。
