CoNiCrMo Particles, but Not TiAlV Particles, Activate the NLRP3 Inflammasome in Periprosthetic Cells

Abstract

Aseptic loosening is the main reason for arthroplasty failure. The wear particles generated at the tribological bearings are thought to induce an inflammatory tissue response, leading to bone loss and the subsequent loosening of the implant. Different wear particles have been shown to activate the inflammasome, thereby contributing to an inflammatory milieu in the direct vicinity of the implant. The aim of this study was to investigate whether the NLRP3 inflammasome is activated by different metal particles in vitro and in vivo. Three different cell lines representing periprosthetic cell subsets (MM6, MG63 and Jurkat) were incubated with different amounts of TiAlV or CoNiCrMo particles. The activation of the NLRP3 inflammasome was determined through the detection of the caspase 1 cleavage product p20 in a Western blot. The formation of the inflammasome was also investigated in vivo using immunohistological staining for ASC in primary synovial tissues as well as tissues containing TiAlV and CoCrMo particles and in vitro after the stimulation of the cells. The results show that the CoCrMo particles induced ASC more markedly, as a readout for inflammasome formation in vivo, compared to TiAlV particular wear. The CoNiCrMo particles also induced ASC-speck formation in all the tested cell lines, which was not induced by the TiAlV particles. The Western blot shows that NRLP3 inflammasome activation, measured through caspase 1 cleavage, was increased only by the CoNiCrMo particles in the MG63 cells. We conclude from our data that the activation of the inflammasome is mainly driven by CoNiCrMo particles and less by TiAlV particles, indicating that different inflammatory pathways are activated by the different alloys.