In vivo morphologic changes in the rat osteoclast induced by gallium nitrate: The result of toxicity or other effects?
In vivo morphologic changes in the rat osteoclast induced by gallium nitrate: The result of toxicity or other effects?
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DOI：
10.1159/000057436
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发表时间：
1999-05-01
期刊：
影响因子：
--
通讯作者：
Singer, FR
中科院分区：
文献类型：
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作者：
Gruber, HE;Norton, HJ;Singer, FR
硝酸镓是一种被批准的抗肿瘤药物，已在临床上应用于治疗癌症相关的高钙血症和佩吉特氏病；然而，其确切的作用机制尚不清楚。目前的研究使用了7天暴露于镓的大鼠，剂量与临床使用的剂量相似。对证实为低钙血症的动物标本进行了破骨细胞超微结构的定量组织形态计量学和超微结构检查。暴露于镓后，破骨细胞发生了惊人的变化。破骨细胞核/破骨细胞数量增加，破骨细胞褶皱边缘沿Howship‘s腔长方向明显减少。破骨细胞数量没有减少，超微结构的变化类型表明，镓的作用机制可能不同于降钙素，降钙素是一种无毒、可逆的抗吸收药物。结果突显了评估镓等试剂对破骨细胞毒性的难度，破骨细胞是一种成熟的分化细胞，不分裂，也不产生特有的细胞外基质成分。
Gallium nitrate, an approved antitumor drug, has found clinical application in the treatment of cancer-related hypercalcemia and of Paget's disease; the exact mechanism of its action, however, remains unknown. The present study utilized rats in a 7-day exposure to gallium at doses similar to those used clinically. Quantitative histomorphometry and ultrastructural examination of osteoclast fine structure were carried out on specimens from animals with documented hypocalcemia. Gallium exposure produced striking changes in the osteoclast. The number of nuclei/osteoclast increased, and the ruffled borders of the osteoclasts were markedly decreased along the length of the Howship's lacunar cavity. The absence of a decrease in osteoclast number and the types of changes seen in ultrastructure suggest that the mechanism of action of gallium seen here may differ from that of calcitonin, a nontoxic, reversible anti-resorbing agent. Results underscore the difficulty in assessing the toxicity of agents such as gallium on the osteoclast, a mature differentiated cell which does not divide and which does not produce a characteristic extracellular matrix component.