Hirashima Y, Ishiguro N, Kondo S, Iwata H
Department of Orthopaedic Surgery, National Higashinagoya Hospital, 101-5 Umemorizaka Meitou-ku, Nagoya, Japan.
J Biomed Mater Res. 2001 Aug;56(2):177-83. doi: 10.1002/1097-4636(200108)56:2<177::aid-jbm1082>3.0.co;2-h.
Polyethylene debris from joint replacements may be transported in synovial fluid and be phagocytosed by macrophages. The activation and migration of macrophages may play important roles in osteolysis and implant loosening. Tissues from the bone-implant interface do not always contain wear debris, which may mean that osteolysis may not require direct contact with wear debris. We hypothesized that the release of polyethylene debris from the implants induces macrophage activation in the joint space. Then the activated macrophages release humoral factors, such as inflammatory cytokines, into the joint fluid. These cytokines may be transported to the bone marrow tissues around the implants where they stimulate the differentiation of the bone marrow cells into osteoclasts. Finally, the activated osteoclasts resorb the surrounding bone. To test this hypothesis, macrophages were stimulated by polyethylene particles. The levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were determined by enzyme-linked immunosorbent assay and were increased significantly. To test humoral interaction between macrophages and bone-marrow cells, a co-culture system was used in an in vitro model. With this system, two kinds of cells can be cultured together with humoral contact without the two cell types having to contact each other. We stimulated the macrophages with 5 microm of polyethylene particles and observed whether the bone marrow cells differentiated into the osteoclasts without contact with the macrophages. The numbers of osteoclasts were assessed using tartrate-resistant acid phosphatase (TRAP) staining. The numbers of TRAP-positive cells in the polyethylene particle-stimulated group were higher than in the control group. The ability of the TRAP-positive cells to resorb bone was confirmed by dentine pit formation assay. The results of this study support our hypothesis and suggest that one mechanism of osteolysis in failed joint arthroplasty is the more distant effects of pro-inflammatory cytokine release on osteoclast differentiation and/or activity.
关节置换术中产生的聚乙烯碎屑可能会在滑液中运输，并被巨噬细胞吞噬。巨噬细胞的激活和迁移可能在骨质溶解和植入物松动中起重要作用。骨-植入物界面的组织并不总是含有磨损碎屑，这可能意味着骨质溶解可能不需要与磨损碎屑直接接触。我们推测，植入物释放的聚乙烯碎屑会诱导关节腔内的巨噬细胞激活。然后，活化的巨噬细胞会向关节液中释放体液因子，如炎性细胞因子。这些细胞因子可能会被运输到植入物周围的骨髓组织，在那里它们会刺激骨髓细胞分化为破骨细胞。最后，活化的破骨细胞会吸收周围的骨质。为了验证这一假设，我们用聚乙烯颗粒刺激巨噬细胞。通过酶联免疫吸附测定法测定白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的水平，结果显示它们显著升高。为了测试巨噬细胞与骨髓细胞之间的体液相互作用，我们在体外模型中使用了共培养系统。利用这个系统，两种细胞可以在体液接触的情况下一起培养，而两种细胞类型无需相互接触。我们用5微米的聚乙烯颗粒刺激巨噬细胞，并观察骨髓细胞在不与巨噬细胞接触的情况下是否会分化为破骨细胞。使用抗酒石酸酸性磷酸酶（TRAP）染色评估破骨细胞的数量。聚乙烯颗粒刺激组中TRAP阳性细胞的数量高于对照组。通过牙本质凹坑形成试验证实了TRAP阳性细胞吸收骨质的能力。本研究结果支持了我们的假设，并表明关节置换失败后骨质溶解的一种机制是促炎细胞因子释放对破骨细胞分化和/或活性产生的更远距离的影响。
