Wang J Y, Wicklund B H, Gustilo R B, Tsukayama D T
Department of Medicine, Hennepin County Medical Center, Minneapolis, MN 55415, USA.
Biomaterials. 1996 Dec;17(23):2233-40. doi: 10.1016/0142-9612(96)00072-5.
Osteolysis has become a major cause of aseptic loosening in total joint arthroplasty (TJA). Titanium, cobalt and chromium are commonly used in orthopaedic implants (e.g. joint prostheses). The release of bone-associated cytokines has been associated with the development of osteolysis in patients with prostheses. We evaluated the effects of these metals on the release of bone-associated cytokines (IL-1 beta, IL-6, TNF-alpha and TGF-beta 1) by human blood monocytes/macrophages and monocyte-like U937 cells upon lipopolysaccharide (LPS) stimulation, the cell proliferation, and their cytotoxic effects on these cells in vitro. We found that the release of IL-1 beta was enhanced by titanium, chromium and cobalt, the release of TNF-alpha was enhanced by titanium and chromium, and the release of IL-6 was enhanced by titanium. All three metal ions inhibited the release of TGF-beta 1. We also found that titanium and chromium, but not cobalt, enhanced blood monocyte/macrophage proliferation in response to LPS while only titanium enhanced U937 cell proliferation in response to LPS. The metals in concentrations ranging from 0.01 to 100 ngml-1 did not stimulate the cells to secrete detectable cytokines in the absence of LPS. Furthermore, a 4-h pre-exposure of blood monocytes/macrophages or U937 cells to the metals did not alter cytokine release when the metals were removed from the media prior to the addition of LPS. Similarly, a 4-h pre-exposure of blood monocytes/macrophages or U937 cells to LPS did not alter cytokine release when LPS was removed from the media prior to the addition of the metals. The metals did not reduce cell viability and induce cell injury after 72h incubation with the cells. The data suggest that the three metals at clinically relevant concentrations modulated cytokine expression, whereas they did not induce any cytotoxic effects. A metal-induced enhancement of bone-resorbing cytokine release with a concomitant inhibition of bone-forming cytokine release may be an important factor in the development of osteolysis, which can severely compromise the outcome of TJA.
骨溶解已成为全关节置换术（TJA）中无菌性松动的主要原因。钛、钴和铬常用于骨科植入物（如关节假体）。假体患者骨相关细胞因子的释放与骨溶解的发生有关。我们评估了这些金属对人血单核细胞/巨噬细胞和单核细胞样U937细胞在脂多糖（LPS）刺激下骨相关细胞因子（IL-1β、IL-6、TNF-α和TGF-β1）释放、细胞增殖以及它们在体外对这些细胞的细胞毒性作用。我们发现钛、铬和钴增强了IL-1β的释放，钛和铬增强了TNF-α的释放，钛增强了IL-6的释放。所有三种金属离子均抑制TGF-β1的释放。我们还发现，钛和铬而非钴增强了血单核细胞/巨噬细胞对LPS的增殖反应，而仅钛增强了U937细胞对LPS的增殖反应。在无LPS的情况下，浓度范围为0.01至100 ng/ml的金属不会刺激细胞分泌可检测到的细胞因子。此外，在添加LPS之前从培养基中去除金属时，血单核细胞/巨噬细胞或U937细胞预先暴露于金属4小时不会改变细胞因子的释放。同样，在添加金属之前从培养基中去除LPS时，血单核细胞/巨噬细胞或U937细胞预先暴露于LPS 4小时也不会改变细胞因子的释放。与细胞孵育7２小时后，这些金属不会降低细胞活力或诱导细胞损伤。数据表明，临床相关浓度的这三种金属调节细胞因子表达，但不会诱导任何细胞毒性作用。金属诱导骨吸收细胞因子释放增强并伴随骨形成细胞因子释放受到抑制，这可能是骨溶解发生的一个重要因素，而骨溶解会严重影响TJA的疗效。
