Role of tumor necrosis factor alpha in particulate-induced bone resorption
Role of tumor necrosis factor alpha in particulate-induced bone resorption
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DOI：
10.1002/jor.1100140107
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发表时间：
1996-01-01
影响因子：
2.8
通讯作者：
Horowitz, SM
中科院分区：
文献类型：
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作者：
Algan, SM;Purdon, M;Horowitz, SM
本研究的目的是确定肿瘤坏死因子α在骨吸收中的作用，骨吸收继发于暴露于骨水泥颗粒的巨噬细胞释放介质。将J774小鼠巨噬细胞系暴露于聚甲基丙烯酸甲酯颗粒24小时，并分析所得条件培养基的前列腺素E（2）、肿瘤坏死因子α、白细胞介素-1 α和β，以及刺激前列腺素E（2）和Ca-45从放射性标记的小鼠颅骨释放的能力。与未暴露的细胞相比，巨噬细胞暴露于聚甲基丙烯酸甲酯颗粒导致肿瘤坏死因子α释放增加9倍（p < 0.01），但未导致前列腺素E（2）、白细胞介素-1 α或白细胞介素-1 β释放显著增加。将巨噬细胞暴露于聚甲基丙烯酸甲酯颗粒30分钟至96小时的时间过程导致肿瘤坏死因子α释放增加，最初在30分钟时检测到，在48小时时达到最大值。巨噬细胞-聚甲基丙烯酸甲酯条件培养基与大鼠颅骨孵育显著增加了骨中Ca-45和前列腺素E（2）的释放。为了研究肿瘤坏死因子α的释放在骨吸收中的作用，在将条件培养基暴露于颅骨之前，将巨噬细胞-聚甲基丙烯酸甲酯条件培养基与抗肿瘤坏死因子α抗体预孵育。这种预孵育成功地显著抑制了颅骨的Ca-45释放（p < 0.01），使其水平与未暴露的颅骨的释放水平没有显著差异。肿瘤坏死因子α似乎在启动颗粒诱导的骨吸收中起关键作用。巨噬细胞暴露于聚甲基丙烯酸甲酯颗粒导致肿瘤坏死因子α以时间依赖性方式显著释放。这种巨噬细胞-聚甲基丙烯酸甲酯条件培养基刺激骨器官培养中前列腺素E（2）的释放和骨吸收。向该体外系统中加入抗肿瘤坏死因子α抗体可抑制巨噬细胞-聚甲基丙烯酸甲酯条件培养基刺激的骨吸收，并部分抑制前列腺素E的产生（2）。在该模型中，颗粒诱导的骨吸收的事件顺序似乎是由巨噬细胞产生肿瘤坏死因子α开始的，随后是骨细胞产生前列腺素E（2），然后是骨吸收。
The purpose of this study was to determine the role of tumor necrosis factor alpha in bone resorption secondary to mediator release from macrophages exposed to cement particles. The J774 mouse macrophage cell line was exposed to polymethylmethacrylate particles for 24 hours and the resulting conditioned medium was analyzed for prostaglandin E(2), tumor necrosis factor alpha, interleukin-l alpha and beta, and the ability to stimulate release of prostaglandin E(2) and Ca-45 from radiolabeled mouse calvaria. Macrophage exposure to polymethylmethacrylate particles led to a 9-fold increase in release of tumor necrosis factor alpha (p < 0.01), but did not lead to a significant increase in release of prostaglandin E(2), interleukin-1 alpha, or interleukin-1 beta when compared to unexposed cells. Exposure of the macrophages to polymethylmethacrylate particles over a time course from 30 minutes to 96 hours led to an increase in the release of tumor necrosis factor alpha that was initially detected at 30 minutes and was maximum at 48 hours. Incubation of the macrophage-polymethylmethacrylate conditioned medium with rat calvaria significantly increased the release of Ca-45 and prostaglandin E(2) from the bone. To study the role of release of tumor necrosis factor alpha in bone resorption, the macrophage-polymethylmethacrylate conditioned medium was then preincubated with anti-tumor necrosis factor alpha antibody prior to exposure of the conditioned medium to the calvaria. This preincubation was successful in significantly inhibiting Ca-45 release by calvaria (p < 0.01) to levels that were not significantly different from the levels of release by unexposed calvaria. Tumor necrosis factor alpha appears to play a critical role in initiating particulate-induced bone resorption. Exposure of macrophages to polymethylmethacrylate particles leads to a significant release of tumor necrosis factor alpha in a time-dependent fashion. This macrophage-polymethylmethacrylate conditioned medium stimulated release of prostaglandin E(2) and bone resorption in bone organ culture. The addition of anti-tumor necrosis factor alpha antibody to this in vitro system inhibited the bone resorption stimulated by the macrophage-polymethylmethacrylate conditioned medium and partially suppressed the production of prostaglandin E(2). The sequence of events in this model for particulate-induced bone resorption appears to be initiated by the production of tumor necrosis factor alpha by the macrophage, followed by production of prostaglandin E(2) by cells in bone, and then by bone resorption.