Glucocorticoids impair bone resorptive activity and viability of osteoclasts disaggregated from neonatal rat long bones.
Glucocorticoids impair bone resorptive activity and viability of osteoclasts disaggregated from neonatal rat long bones.
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糖皮质激素损害从新生大鼠长骨中分解的破骨细胞的骨吸收活性和活力。
DOI：
10.1210/endo-125-3-1290
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发表时间：
1989
期刊：
影响因子：
4.8
通讯作者：
T. Chambers
中科院分区：
文献类型：
--
作者：
J. Tobias;T. Chambers
一般认为，糖皮质激素通过减少骨形成和增加骨吸收的组合引起骨质疏松症。然而，糖皮质激素对破骨细胞的直接影响尚未确定。因此，我们测试了氢化可的松和地塞米松对破骨细胞从新生大鼠长骨分解的骨吸收的影响。氢化可的松和地塞米松分别在10（-7）至10（-5）M和10（-9）至10（-6）M范围内对骨吸收产生剂量依赖性抑制，浓度可能发生在治疗和疾病期间。发现骨吸收的抑制与破骨细胞存活受损有关：10（-6）M氢化可的松和10（-7）M地塞米松使破骨细胞数量减少至对照值的约25%。破骨细胞的糖皮质激素的细胞毒性完全拮抗孕酮，这本身对破骨细胞的生存没有影响。对这些抑制作用的时程分析显示，6 h时存活率无显著降低，12 h时存活率显著抑制。我们不能检测到破骨细胞形态学的特异性变化与这种受损的生存能力。糖皮质激素对破骨细胞活力损害的相对效力与其结合糖皮质激素受体的相对亲和力相似，这与孕酮的抑制作用一起表明了受体介导的机制。糖皮质激素的这种受体介导的细胞毒性作用以前仅在淋巴样细胞中有报道。破骨细胞对糖皮质激素致死作用的敏感性表明糖皮质激素可能在生理学上作为骨吸收抑制剂发挥作用。
It is generally believed that glucocorticoids cause osteoporosis through a combination of decreased bone formation and increased bone resorption. However, the direct effect of glucocorticoids on osteoclasts has not been determined. We therefore tested the effects of hydrocortisone and dexamethasone on bone resorption by osteoclasts disaggregated from neonatal rat long bones. Hydrocortisone and dexamethasone caused a dose-dependent inhibition of osteoclastic bone resorption in the range 10(-7) to 10(-5) M, and 10(-9) to 10(-6) M, respectively, at concentrations likely to occur during therapy and disease. Inhibition of bone resorption was found to be associated with impaired osteoclast survival: osteoclast numbers were reduced to approximately 25% of control values by 10(-6) M hydrocortisone and 10(-7) M dexamethasone. Osteoclast cytotoxicity by glucocorticoids was completely antagonized by progesterone, which itself had no effect on osteoclast survival. Analysis of the time course of these inhibitory effects showed a nonsignificant reduction in survival by 6 h and marked inhibition of survival by 12 h. We could detect no specific changes in osteoclast morphology in association with this impaired viability. The relative potencies of the glucocorticoids for impairment of osteoclast viability was similar to their relative affinities for binding the glucocorticoid receptor, and this, together with inhibition by progesterone, suggests a receptor-mediated mechanism. Such a receptor-mediated cytotoxic action of glucocorticoids has only previously been reported with lymphoid cells. The sensitivity of osteoclasts to the lethal effects of glucocorticoids suggests that glucocorticoids may have a role in physiology as inhibitors of osteoclastic bone resorption.
大鼠脑室内注射重组人白细胞介素-1 诱导促肾上腺皮质激素释放：前列腺素可能参与。
影响因子：
4.8
作者：
Katsuura,G;Gottschall,PE;Dahl,RR;Arimura,A
通讯作者：
Arimura,A