Distinct Inflammatory Gene Pathways Induced by Particles

Abstract

The biologic response to particulate load after arthroplasty has not been fully characterized but is believed mediated by proinflammatory cytokines released from mononuclear cells in the periprosthetic region. To investigate the contribution of lymphocytes to expression of proinflammatory genes induced by metal particles, we compared gene expression of mononuclear cells in response to metal and polymethylmethacrylate particles using cDNA microarray profiling. Peripheral blood mononuclear cells and monocytes were stimulated with polymethylmethacrylate and titanium particles of clinically relevant sizes. Polymethylmethacrylate elicited a six- to 12-fold increase in gene expression of tumor necrosis factor alpha, interleukin 1alpha, interleukin 1beta, interleukin 6, and interleukin 8 in purified monocytes and unfractionated peripheral blood mononuclear cells. Although the effect of titanium on stimulation of purified monocytes was modest, stimulation of lymphocyte-containing peripheral blood mononuclear cells by titanium particles resulted in monocyte-derived proinflammatory cytokine expression. In contrast to polymethylmethacrylate, titanium particles stimulated increased expression of T lymphocyte-derived cytokines, including interleukin 2, interferon gamma, interleukin 9, and interleukin 22, in peripheral blood mononuclear cell cultures. The induction of T cell activation by titanium particles suggests lymphocytes may contribute to the inflammation that mediates osteolysis in patients with metallic particulate debris after total joint replacement.

Risk factors for accelerated polyethylene wear and osteolysis in ABG I total hip arthroplasty

“…Finally, our finding that higher PE wear rates are associated with a risk of severe osteolysis at both the acetabular and femoral sites is in accord with the literature [21,38]; this finding strongly supports particle disease as the leading mechanism of osteolysis initiation and expansion [1]. On the other hand, the main limitation of our study is that it is based on an implant especially prone to rapid wear and the initiation of OL.…”

“…Debris from polyethylene (PE) wear is believed to be a key factor in the development of osteolysis around total hip arthroplasty (THA) [1]. This debris triggers multiple adverse host reactions that involve signalling pathways and finally result in osteoclast-mediated bone resorption [2].…”

Review of periprosthetic osteolysis in total joint arthroplasty: An emphasis on host factors and future directions

“…As has been demonstrated in the literature, IL-1b has been intimately linked to osteolysis; to the extent of being used a secondary measure of periprosthetic bone resorption in several studies. [8][9][10][11][12][13][14][15]17,57,74,75 The activation of cytokine released by uric acid crystals in gout is similar to wear-debris particles activation an immune response in the setting of aseptic loosening, and therefore lies the potential benefit of these pharmacologics in periprosthetic osteolysis. A recent study has also REVIEW OF PERIPROSTHETIC OSTEOLYSIS proposed that the prophylactic administration of erythromycin may maximize the longevity of a prosthetic joint by lessening, or at least delaying, the effects of osteolysis immediately adjacent to the implanted construct.…”

“…16 Wear-debris activation of mitogen-activated protein (MAP) kinase cascades, RANKL, and a multitude of other transcription factors is the vehicle by which periprosthetic bone destruction and resorption occurs. [17][18][19][20] Nonetheless, it is recognized that osteolysis is a multifactorial process with implant materials and host factors playing a significant role.…”

Periprosthetic osteolysis

“…It remains the leading complication of total joint arthroplasty (Pearle et al, 2007), often resulting in aseptic loosening of the implant, and ultimately requiring revision surgery (Greenfield et al, 2002).…”