Department of Orthopaedic Surgery, Otto-von-Guericke-University, 39120 Magdeburg, Germany.
Institute of Materials and Joining Technology, Otto-von-Guericke-University, 39120 Magdeburg, Germany.
Int J Mol Sci. 2023 Mar 7;24(6):5108. doi: 10.3390/ijms24065108.
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.
无菌性松动是关节置换失败的主要原因。在摩擦学轴承处产生的磨损颗粒被认为会引发炎症组织反应，导致骨质流失和随后植入物松动。不同的磨损颗粒已被证明能激活炎性小体，从而有助于在植入物的直接附近形成炎症环境。本研究旨在探讨 NLRP3 炎性小体是否会被不同的金属颗粒在体外和体内激活。用不同数量的 TiAlV 或 CoNiCrMo 颗粒孵育三种代表假体周围细胞亚群的细胞系（MM6、MG63 和 Jurkat）。通过 Western blot 检测 caspase 1 裂解产物 p20 来确定 NLRP3 炎性小体的激活。还通过对原发性滑膜组织以及含有 TiAlV 和 CoCrMo 颗粒的组织中 ASC 的免疫组织化学染色以及细胞刺激后的体外试验来研究炎性小体的形成。结果表明，与 TiAlV 颗粒相比，CoCrMo 颗粒更能诱导 ASC，作为体内炎性小体形成的指标。CoNiCrMo 颗粒还能诱导所有测试的细胞系中 ASC 斑点形成，而 TiAlV 颗粒则不能。Western blot 显示，仅 CoNiCrMo 颗粒能在 MG63 细胞中通过 caspase 1 切割增加 NLRP3 炎性小体的激活。我们从数据中得出结论，炎性小体的激活主要是由 CoNiCrMo 颗粒驱动，而 TiAlV 颗粒的驱动作用较小，这表明不同的合金会激活不同的炎症途径。
