Receptor activator of nuclear factor κB ligand is expressed in resident and inflammatory cells in aseptic and septic prosthesis loosening
Receptor activator of nuclear factor κB ligand is expressed in resident and inflammatory cells in aseptic and septic prosthesis loosening
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DOI：
10.1080/03009740310003929
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发表时间：
2003-10-01
影响因子：
2.1
通讯作者：
Krenn, V
中科院分区：
文献类型：
--
作者：
Gehrke, T;Sers, C;Krenn, V
目的：无菌性和感染性假体松动导致假体周围骨丢失的发病机制尚不清楚。有相当多的证据表明，巨噬细胞和破骨细胞在假体周围的局灶性骨侵蚀和骨质溶解中起关键作用。RANKL（receptor activator of nuclear factor kappaB ligand，核因子κ B配体受体激活因子）是一种有效的破骨细胞生成因子，参与骨髓瘤和类风湿性关节炎患者的骨破坏。骨保护素（OPG）是天然的RANKL抑制剂，可预防假体周围骨丢失。方法：采用免疫组化和免疫印迹法检测5例感染性松动和6例无菌性松动假体周围界面RANKL及其受体RANK和OPG的表达和分布。此外，炎性浸润的免疫表型测定[CD 3，CD 68，Ki-67，抗酒石酸酸性磷酸酶（TRAP）]。然而，在所有情况下，RANKL和RANK可在巨噬细胞和巨细胞中显示。此外，通过免疫印迹分析检测的RANKL证明与用作对照的重组RANKL具有相同的分子量（31 kappaD和约48 kappaD）。在无菌性松动中检测到OPG，其中巨噬细胞显示强染色，但多核巨细胞仅弱染色。结论：脓毒性松动中骨丢失的发病机制尚不清楚，因为脓毒性松动中的巨噬细胞和巨细胞很少，其中一半表达OPG。在无菌性松动中，由于OPG表达，巨噬细胞可能不受RANKL刺激。但多核巨细胞可能被激活，因为它们几乎不表达OPG。由于RANKL和RANK的表达，它们可能是无菌性松动中假体周围骨丢失的原因。
Objective: The pathogenesis of periprosthetic bone loss in aseptic and septic prosthesis loosening is unclear. There is considerable evidence that macrophages and osteoclasts play a key role in focal bone erosion and osteolysis around the prosthesis. RANKL (receptor activator of nuclear factor kappaB ligand) was shown to be a potent osteoclastogenic factor, and to be involved in bone destruction of myeloma and rheumatoid arthritis patients. Osteoprotegerin (OPG) is the natural RANKL inhibitor and may prevent periprosthetic bone loss.Methods: The presence and distribution of RANKL, its receptor RANK and OPG in the periprosthetic interface of septically (n=5) and aseptically (n=6) loosened prostheses was examined by immunohistochemistry and immunoblotting. Additionally, the immunophenotype of the inflammatory infiltrate was determined [CD3, CD68, Ki-67, tartrate-resistant acid posphatase (TRAP)].Results: Aseptic and septic cases revealed a different histopathologic pattern. However, in all cases RANKL and RANK could be demonstrated in macrophages and giant cells. In addition, RANKL detected by immunoblot analysis proved to have the same molecular weight as a recombinant RANKL used as a control (31 kappaD and approximately 48 kappaD). OPG was detected in aseptic loosening, where macrophages showed a strong staining, but multinucleated giant cells were only weakly stained. A weak OPG staining was also observed in septic loosening.Conclusion: The pathogenesis of bone loss in septic loosening remains unclear, because the septic membrane bears few macrophages and giant cells, and half of them express OPG. In aseptic loosening, macrophages might not be stimulated by RANKL as a result of OPG expression. But multinucleated giant cells may be activated, as they hardly express OPG. They might be responsible for periprosthetic bone loss in aseptic loosening as a result of their RANKL and RANK expression.