Evidence for an autocrine/paracrine role for interleukin-6 in bone resorption by giant cells from giant cell tumors of bone.
Evidence for an autocrine/paracrine role for interleukin-6 in bone resorption by giant cells from giant cell tumors of bone.
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DOI：
10.1210/endo.131.5.1425421
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发表时间：
1992-11
期刊：
影响因子：
4.8
通讯作者：
Y. Ohsaki;S. Takahashi;T. Scarcez;A. Demulder;T. Nishihara;R. Williams;G. Roodman
中科院分区：
文献类型：
--
作者：
Y. Ohsaki;S. Takahashi;T. Scarcez;A. Demulder;T. Nishihara;R. Williams;G. Roodman
白细胞介素-6（IL-6）是一种多功能细胞因子，其在骨细胞骨吸收中的作用尚未明确。因此，我们使用了巨细胞，表达破骨细胞的许多功能，从骨巨细胞瘤作为模型，以检查IL-6可能发挥的作用，在人类骨细胞骨吸收。我们发现，来自高度纯化的巨细胞（10（6）/ml）的24小时培养物的条件培养基含有大量的IL-6（37.9 +/- 8.8 ng/ml），与肿瘤基质细胞产生的IL-6的量（29.8 +/- 11.5 ng/ml）相似。巨细胞瘤巨细胞和基质细胞表达IL-6 mRNA，如聚合酶链反应分析和原位杂交研究所示，免疫组化技术表明，巨细胞表达IL-6受体。添加IL-6中和抗体可显著降低纯化巨细胞对牙本质的吸收面积，且呈剂量依赖性，添加IL-6可恢复纯化巨细胞的吸收能力。这些数据表明，IL-6可能作为一个自分泌和旁分泌因子的人破骨细胞和这些细胞的骨吸收能力发挥重要作用。
Interleukin-6 (IL-6) is a multifunctional cytokine whose role in osteoclastic bone resorption has not been clearly defined. Therefore, we have used giant cells, which express many features of osteoclasts, from giant cell tumors of bone as a model to examine the role that IL-6 may play in human osteoclastic bone resorption. We found that conditioned medium from 24-h cultures of highly purified giant cells (10(6)/ml) contained large amounts of IL-6 (37.9 +/- 8.8 ng/ml), similar to the amount of IL-6 produced by tumor stromal cells (29.8 +/- 11.5 ng/ml). Giant cells and stromal cells from giant cell tumors expressed IL-6 mRNA, as indicated by polymerase chain reaction analysis and in situ hybridization studies, and immunohistochemical techniques demonstrated that the giant cells expressed IL-6 receptors. The addition of a neutralizing antibody to IL-6 significantly decreased the area of dentine resorbed by purified giant cells in a dose-dependent manner, and the addition of IL-6 to cultures of purified giant cells pretreated with anti-IL-6 restored the resorbing capacity of the giant cells. These data suggest that IL-6 may act as both an autocrine and a paracrine factor for human osteoclasts and play an important role in the bone-resorbing capacity of these cells.