MusculoskeletalUp-Regulated Expression of MIF by Interfacial Membrane Fibroblasts and Macrophages Around Aseptically Loosened Implants
Introduction
Total joint replacement is an effective treatment for the end-stage destructive arthropathy. It not only restores the function of the joint, but also relieves pain. In the past 20 y, it has been widely used for treating arthropathy. However, with passing time, the aseptic loosening of the implants occurs in some artificial joints, which leads to failure of the artificial joints long-term. The causes of aseptic loosening of the implants maybe include micromotion between the bone and implants, local mechanical stresses, and the cellular host response to wear debris of implants, which induces local inflammation. Moreover, the wear debris, inducing a local chronic inflammatory reaction, plays an important role in the process of aseptic loosening of implants. The interfacial membranes, mainly including fibroblasts and macrophages, are always detected at the interface of the bone and the aseptically loosened implant. These cells may produce multiple proinflammatory cytokines, such as tumor necrosis factor alpha (TNFα), interleukin 6 (IL-6), and matrix metalloproteinases (MMPs), which induce local inflammation and take part in the process of aseptic loosening of implants 1, 2, 3. On the other hand, as an important proinflammatory cytokine, macrophage migration inhibitory factor (MIF) can up-regulate the expression of other proinflammatory cytokines, such as TNFα and IL-6. MIF was found in synovium of rheumatoid arthritis (RA) of knee joints and it was proven that MIF was a significant regulator of inflammatory diseases [4]. Although the morphology and biology are similar between synoviocytes of RA and aseptically loosened artificial joint, the pathogenesis of the diseases is different 5, 6. It is unknown if MIF mediates the inflammatory process during aseptic loosening of implants after total joint replacement. Here, we carried out this study to investigate if the cells in the interfacial membranes produce MIF.
Section snippets
Patients
The 15 tissue samples of interfacial membranes were obtained from the tissues around the aseptically loosened femoral implants adjacent to osteolytic lesion in 15 patients who had undergone revision total hip replacement because of aseptic loosening of implants. None of the patients had clinical, biochemical, or operative findings that would have indicated bacterial infections of the artificial hip joints. None of the patients had any major technical problems, such as femoral misalignment.
Results
As shown in Fig. 1A and B, the histologic evaluation revealed that morphologically, at least three types of cells were observed in the interfacial membrane tissues from the artificial joints of aseptically loosened implants, including mononuclear-macrophage cells, multinucleated giant cells, and fibroblasts. Wear particles were surrounded by multinucleated giant cells (Fig. 1B). As shown in Fig. 1C and D, mononuclear-macrophage cells and fibroblasts were observed in the synovium from hip joints
Discussion
This study demonstrated an increased expression of MIF protein and mRNA in the interfacial membranes from artificial hip joints of aseptically loosened implants compared with synovium from hip joints of fresh femoral neck fracture. Moreover, it was first demonstrated that the fibroblasts in the interfacial membrane expressed MIF, and the number of fibroblasts immunoreactive with anti-MIF antibody in interfacial membrane was higher than in the control synovium. This indicated that the increased
Acknowledgments
This work was supported by the Shanghai Municipal Health Bureau Science Fund (2010QJ036A), the National natural Science Fund of China (81171688), and the combined medical knowledge of the Engineering Foundation of Shanghai Jiao Tong University (YG2010MS33).
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