These data clearly demonstrate production of cytokines by T cells in RA synovial tissue, indicating that activated T cells play a role in the pathophysiological events of RA.
The differential use of anatomic and reversed shoulder prostheses in secondary fracture treatment leads to an improvement in postoperative results. In fracture sequelae types 1 and 2, the anatomic prosthesis is a better choice. However, in fracture sequelae types 3 and 4 with severe deformities, the reversed prosthesis is clearly superior to the anatomic prosthesis.
Objective
To investigate the expression of the transcription factor Ets‐1 in synovial tissue and cultured synovial fibroblasts from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to study the regulation of Ets‐1 expression and activation in synovial fibroblasts by proinflammatory cytokines.
Methods
In situ expression of Ets‐1 in synovial tissue from RA and OA patients was examined by double immunohistochemistry. The effects of interleukin‐1 (IL‐1) or tumor necrosis factor α (TNFα) on Ets‐1 expression and activation (DNA binding) in cultured synovial fibroblasts were analyzed by Western blotting and DNA gel shift assay, respectively. In addition, the intracellular location of Ets‐1 in synovial fibroblasts was determined by immunofluorescence.
Results
Pronounced expression of Ets‐1 was detected in synovial tissues from all RA patients evaluated, particularly in the synovial lining layer and the sublining areas. Ets‐1 was expressed by both fibroblasts and macrophages as well as by endothelial cells, while only a few T cells stained positive for Ets‐1. In synovial specimens from OA patients, Ets‐1 expression was much less frequently observed and was largely restricted to vascular cells. Ets‐1 was expressed to a similar degree in cultured synovial fibroblasts from RA and OA patients, as demonstrated by reverse transcriptase–polymerase chain reaction and Western blotting. Both IL‐1 and TNFα induced pronounced up‐regulation of Ets‐1 in synovial fibroblasts. Moreover, binding of Ets‐1 to its specific DNA binding site was induced by both cytokines, although with different time courses. Immunofluorescence staining revealed a dominant nuclear localization of Ets‐1 in IL‐1– or TNFα‐stimulated synovial fibroblasts.
Conclusion
The overexpression of Ets‐1 observed in RA synovial tissue appears to be caused by TNFα and IL‐1, suggesting that Ets‐1 may be an important factor in the cytokine‐mediated inflammatory and destructive cascade characteristic of RA.
In this review the involvement of T cells, in addition to that of the monocyte/macrophage lineage, in the pathogenesis of rheumatoid arthritis is discussed. The evidence for the pathogenetic importance of T cells is based upon their state of activation in the synovial membrane and the cytokines produced. These cytokines can be detected in synovial fluids as well as in the synovial membrane by both immunohistochemistry and in situ hybridization. However, cytokine production can be detected only in a minor fraction of the T cells which contrasts the number of non-T cells observed to synthesize cytokines. Nevertheless, it can be assumed that the small amount of lymphokines is sufficient to activate a cytokine cascade derived from other cells. The cytokine profile secreted is indicative for a T cell response that primarily involves Th1-like cells.
The postmortem findings of osteolysis and/or lymphocytic infiltration associated with eight clinically well-functioning, low wear devices (a total wear rate of <4 microm/yr) suggest there may be frequent, unappreciated femoral bone loss and local immunological response in patients with second-generation metal-on-metal hip implants. Compared with previous postmortem studies, our findings showed the extent of osteolysis was similar to that with metal-on-polyethylene articulations.
Cementless acetabular fixation has demonstrated superior long-term durability in total hip replacement, but most series have studied implants with porous metal surfaces. We retrospectively evaluated the results of 100 consecutive patients undergoing total hip replacement where a non-porous Allofit component was used for primary press-fit fixation. This implant is titanium alloy, grit-blasted, with a macrostructure of forged teeth and has a biradial shape. A total of 81 patients (82 hips) were evaluated at final follow-up at a mean of 10.1 years (8.9 to 11.9). The Harris Hip Score improved from a mean 53 points (23 to 73) pre-operatively to a mean of 96 points (78 to 100) at final review. The osseointegration of all acetabular components was radiologically evaluated with no evidence of loosening. The survival rate with revision of the component as the endpoint was 97.5% (95% confidence interval 94 to 100) after 11.9 years. Radiolucency was found in one DeLee-Charnley zone in four acetabular components. None of the implants required revision for aseptic loosening. Two patients were treated for infection, one requiring a two-stage revision of the implant. One femoral stem was revised for osteolysis due to the production of metal wear debris, but the acetabular shell did not require revision. This study demonstrates that a non-porous titanium acetabular component with adjunct surface fixation offers an alternative to standard porous-coated implants.
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