Synergistic effect of particles and cyclic pressure on cytokine production in human monocyte/macrophages: Proposed role in periprosthetic osteolysis

Synergistic effect of particles and cyclic pressure on cytokine production in human monocyte/macrophages: Proposed role in periprosthetic osteolysis
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DOI:
10.1016/s8756-3282(01)00658-5
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发表时间:
2002-01-01
期刊:
影响因子:
4.1
通讯作者:
Andrew, JG
Andrew, JG
中科院分区:
医学2区
文献类型:
--
作者:
McEvoy, A;Jeyam, M;Andrew, JG

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由颗粒磨损碎屑激活的大骨溶解在关节植入物松动期间发生的骨质溶解过程中非常重要。我们先前发现,在0.138 MPa的循环压力下,培养的巨噬细胞中白细胞介素-1 β(IL-1 β)、IL-6和肿瘤坏死因子-α的水平升高,这表明循环压力可能是巨噬细胞活化的另一个相关原因。本研究首先研究了一系列循环压力对培养的巨噬细胞的影响,包括细胞因子表达的时间过程的研究。在0.138 MPa,TNF-α的上清液水平最大在12小时,而IL-6和IL-1 β最大在24 It。所有四个循环压力水平测试(无颗粒)导致所有三种细胞因子的生产增加相对于对照。这些增加在0.069和0.035 MPa下最显著,并且在0.017 MPa下细胞因子产生的增加在统计学上不显著。进一步的研究表明,来自循环加压巨噬细胞的条件培养基在新生小鼠颅骨测定系统中刺激骨吸收。从加压单核细胞的条件培养基中培养的颅盖骨释放的钙水平增加,显微镜下观察到抗酒石酸酸性磷酸酶阳性破骨细胞增加。由于颗粒磨损碎屑在植入物松动中很重要,因此还将超高分子量聚乙烯颗粒添加到加压细胞培养物中。实验比较了大气压力、单独的循环压力、单独的颗粒以及颗粒和循环压力组合的效果。超高分子量聚乙烯颗粒和0.017 MPa循环压力的组合导致所有三种细胞因子的水平与单独使用压力或颗粒所发现的水平相比显著协同升高。我们认为,单核细胞/巨噬细胞激活的周期性压力发挥了重要作用,在骨溶解中看到植入物的无菌性松动。观察到的颗粒和压力之间的协同效应可加速植入物松动,这意味着循环压力(通过改善植入物固定)或磨屑载荷的降低可减少骨质溶解。(C)2002年,Elsevier Science Inc. All rights reserved.
Macrophages, activated by particulate wear debris, are important in the process of osteolysis, which occurs during joint implant loosening. We previously found increased levels of interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha in cultured macrophages subjected to cyclical pressure of 0.138 MPa, suggesting that cyclic pressure may be another relevant cause of macrophage activation. The current study first investigated the effects of a range of cyclic pressures on cultured macrophages, including an investigation of the time course of cytokine expression. At 0.138 MPa, supernatant levels of TNF-alpha were maximal at 12 h, whereas IL-6 and IL-1beta were maximal at 24 It. All four cyclic pressure levels tested (without particles) resulted in increased production of all three cytokines relative to control. These increases were most marked at 0.069 and 0.035 MPa, and the increase in cytokine production at 0.017 MPa was not statistically significant. Further studies demonstrated that conditioned media from cyclically pressurized macrophages stimulated bone resorption in a neonatal mouse calvarial assay system. There were increased levels of calcium released from calvaria cultured in conditioned media from pressurised monocytes, and an increase in tartate-resistant acid phosphatase-positive osteoclasts was observed microscopically. As particulate wear debris is important in implant loosening, ultra high molecular weight polyethylene particles were also added to the pressurized cell cultures. The experiments compared the effect of atmospheric pressure, cyclic pressure alone, particles alone, and particles and cyclic pressure combined. A combination of ultra high molecular weight polyethylene particles and cyclic pressure at 0.017 MPa resulted in a dramatic synergistic elevation of levels of all three cytokines compared with the levels found with either pressure or particles alone. We propose that monocyte/macrophage activation by cyclic pressure plays a major role in the osteolysis seen in aseptic loosening of implants. The synergistic effect observed between particles and pressure could accelerate implant loosening, and implies that reduction in either cyclic pressure (by improving implant fixation) or wear debris load would reduce osteolysis. (C) 2002 by Elsevier Science Inc. All rights reserved.