Glucocorticoids inhibit bone resorption by isolated rat osteoclasts by enhancing apoptosis

Glucocorticoids inhibit bone resorption by isolated rat osteoclasts by enhancing apoptosis
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DOI:
10.1677/joe.0.1540397
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发表时间:
1997-09-01
影响因子:
4
通讯作者:
Antakly, T
Antakly, T
中科院分区:
医学2区
文献类型:
--
作者:
Dempster, DW;Moonga, BS;Antakly, T

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本文研究了糖皮质激素对体外培养的新生大鼠破骨细胞活性和存活率的影响。在骨切片分析中,糖皮质激素引起骨吸收量的剂量依赖性减少,同时伴有破骨细胞数量的平行减少。破骨细胞的丢失是由于它们的死亡,这是通过凋亡过程发生的。后者的证据是通过一系列技术获得的,包括延时视频显微镜、吖啶橙子染色、DNA片段检测和透射电子显微镜。免疫细胞化学显示破骨细胞中存在糖皮质激素受体,糖皮质激素受体拮抗剂RU486可以阻止糖皮质激素诱导的细胞死亡。这些观察结果表明,糖皮质激素促进受体介导的大鼠破骨细胞在体外凋亡。这一发现可能有助于解释最近的数据表明,与其对人体骨骼的影响形成鲜明对比,糖皮质激素抑制骨吸收,增加骨量在大鼠体内。
We have studied the effects of glucocorticoids on the activity and viability of neonatal rat osteoclasts in vitro. In the bone slice assay, glucocorticoids caused a dose-dependent decrease in the amount of bone resorbed, which was accompanied by a parallel decrease in osteoclast number. Loss of osteoclasts was due to their death, which occurred by the process of apoptosis. Evidence for the latter was obtained by a range of techniques, including time-lapse video microscopy, acridine orange staining, DNA fragment detection and transmission electron microscopy. Immunocytochemistry revealed the presence of glucocorticoid receptors in osteoclasts, and glucocorticoid-induced cell death could be prevented by the glucocorticoid receptor antagonist, RU486. These observations suggest that glucocorticoids promote receptor-mediated apoptosis of rat osteoclasts in vitro. This finding may help to explain recent data indicating that, in sharp contrast with their effects on the human skeleton, glucocorticoids inhibit bone resorption and increase bone mass in rats in vivo.