Landgraeber Stefan, Toetsch Martin, Wedemeyer Christian, Saxler Guido, Tsokos Michael, von Knoch Fabian, Neuhäuser Markus, Löer Franz, von Knoch Marius
Department of Orthopaedics, University of Duisburg-Essen, Pattbergstrasse 1-3, 45239 Essen, Germany.
Biomaterials. 2006 May;27(15):3010-20. doi: 10.1016/j.biomaterials.2006.01.006. Epub 2006 Jan 30.
Particle-induced osteolysis is a major cause of aseptic loosening after total joint replacement. The possible induction of apoptosis has not been addressed in great detail. Thus far, it has been shown that ceramic and polyethylene particles can induce apoptosis of macrophages in vitro. The purpose of this study was to test the hypothesis that wears debris generated from total hip arthroplasty could induce cellular damage and apoptosis in vivo. We therefore determined by immunohistochemical methods if increased expression of p53, an important transcription factor, and BAK and Bcl-2, two important regulators of apoptosis, can be found in interface membranes and capsules of hips with aseptically loose implants. Strongly positive immunohistochemical staining for p53 and BAK was found in peri-implant tissues from patients with aseptic hip implant loosening. Differentiation of various cell types showed that macrophages stained positive for p53 in all capsule and interface specimens. p53 was frequently detected in giant cells. Positive staining of BAK in macrophages and giant cells was seen in all specimens. Some positive reactions were observed in fibroblasts, only two of 19 cases stained for p53 and three cases for BAK within synovial cells. Positive macrophages and giant cells were localized around polyethylene particles. While T-lymphocytes showed a regular BAK-staining, the other leukocytes were negative. Statistical analyses showed significant positive correlations (p < 0.001) between the presence of polyethylene and metal debris and the expression of BAK and p53. Polyethylene particles were surrounded by more positive macrophages and giant cells than were metal particles, indicating that polyethylene debris may be a stronger inductor of cell cycle arrest and apoptosis than metal debris. In this study apoptosis of macrophages, giant cells and T-lymphocytes in capsules and interface membranes of patients with aseptic hip implant loosening has been demonstrated in vivo. It is possible that the apoptotic cascade could evolve as a novel therapeutic target to prevent particle-induced osteolysis.
颗粒诱导的骨溶解是全关节置换术后无菌性松动的主要原因。关于细胞凋亡的可能诱导作用尚未得到详细研究。迄今为止，已有研究表明陶瓷和聚乙烯颗粒可在体外诱导巨噬细胞凋亡。本研究的目的是验证全髋关节置换术产生的磨损碎屑可在体内诱导细胞损伤和凋亡这一假说。因此，我们采用免疫组化方法检测了在无菌性松动植入物的髋关节界面膜和关节囊中，重要转录因子p53以及凋亡的两个重要调节因子BAK和Bcl-2的表达是否增加。在无菌性髋关节植入物松动患者的植入物周围组织中发现了p53和BAK的强阳性免疫组化染色。对各种细胞类型的分化显示，在所有关节囊和界面标本中，巨噬细胞p53染色呈阳性。在巨细胞中经常检测到p53。在所有标本中均可见巨噬细胞和巨细胞中BAK染色呈阳性。在成纤维细胞中观察到一些阳性反应，滑膜细胞中19例仅有2例p53染色阳性，3例BAK染色阳性。阳性巨噬细胞和巨细胞定位于聚乙烯颗粒周围。虽然T淋巴细胞显示出规则的BAK染色，但其他白细胞为阴性。统计分析表明，聚乙烯和金属碎屑的存在与BAK和p53的表达之间存在显著正相关（p < 0.001）。聚乙烯颗粒周围的阳性巨噬细胞和巨细胞比金属颗粒更多，表明聚乙烯碎屑可能比金属碎屑更能诱导细胞周期停滞和凋亡。在本研究中，已在体内证实了无菌性髋关节植入物松动患者关节囊和界面膜中的巨噬细胞、巨细胞和T淋巴细胞凋亡。凋亡级联反应有可能发展成为预防颗粒诱导的骨溶解的新治疗靶点。
