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Activation of synovial fibroblasts from patients at revision of their metal-on-metal total hip arthroplasty.
Particle and Fibre Toxicology ( IF 10 ) Pub Date : 2020-08-27 , DOI: 10.1186/s12989-020-00374-y
Jing Xu 1, 2 , Junyao Yang 2, 3 , Jian Chen 4 , Xiaoli Zhang 2 , Yuanhao Wu 2 , Alister Hart 5 , Agata Nyga 6, 7 , Julia C Shelton 2
Affiliation  

The toxicity of released metallic particles generated in metal-on-metal (MoM) total hip arthroplasty (THA) using cobalt chromium (CoCr) has raised concerns regarding their safety amongst both surgeons and the public. Soft tissue changes such as pseudotumours and metallosis have been widely observed following the use of these implants, which release metallic by-products due to both wear and corrosion. Although activated fibroblasts, the dominant cell type in soft tissues, have been linked to many diseases, the role of synovial fibroblasts in the adverse reactions caused by CoCr implants remains unknown. To investigate the influence of implants manufactured from CoCr, the periprosthetic synovial tissues and synovial fibroblasts from patients with failed MoM THA, undergoing a revision operation, were analysed and compared with samples from patients undergoing a primary hip replacement, in order to elucidate histological and cellular changes. Periprosthetic tissue from patients with MoM implants was characterized by marked fibrotic changes, notably an increase in collagen content from less than 20% to 45–55%, an increase in α-smooth muscle actin positive cells from 4 to 9% as well as immune cells infiltration. Primary cell culture results demonstrated that MoM synovial fibroblasts have a decreased apoptosis rate from 14 to 6% compared to control synovial fibroblasts. In addition, synovial fibroblasts from MoM patients retained higher contractility and increased responsiveness to chemotaxis in matrix contraction. Their mechanical properties at a single cell level increased as observed by a 60% increase in contraction force and higher cell stiffness (3.3 kPa in MoM vs 2.18 kPa in control), as measured by traction force microscopy and atomic force microscopy. Further, fibroblasts from MoM patients promoted immune cell invasion by secreting monocyte chemoattractant protein 1 (MCP-1, CCL2) and induced monocyte differentiation, which could also be associated with excess accumulation of synovial macrophages. Synovial fibroblasts exposed in vivo to MoM THA implants that release CoCr wear debris displayed dramatic phenotypic alteration and functional changes. These findings unravelled an unexpected effect of the CoCr alloy and demonstrated an important role of synovial fibroblasts in the undesired tissue reactions caused by MoM THAs.

中文翻译:

在金属对金属全髋关节置换术的修订版中激活患者的滑膜成纤维细胞。

在金属对金属(MoM)的全髋关节置换术(THA)中使用钴铬(CoCr)产生的释放金属颗粒的毒性引起了外科医生和公众对其安全性的关注。使用这些植入物后,已广泛观察到诸如假瘤和金属化病的软组织变化,这些植入物由于磨损和腐蚀而释放出金属副产物。尽管活化的成纤维细胞是软组织中占主导地位的细胞类型,已与许多疾病相关,但滑膜成纤维细胞在CoCr植入物引起的不良反应中的作用仍然未知。为了研究由CoCr制造的植入物,MoM THA失败患者的修复手术中的假体周围滑膜组织和滑膜成纤维细胞的影响,为了阐明组织学和细胞学变化,分析并与接受初次髋关节置换术的患者的样品进行了比较。MoM植入物患者的假体周围组织的特征是明显的纤维化改变,尤其是胶原含量从不到20%增加到45-55%,α平滑肌肌动蛋白阳性细胞从4%增加到9%以及免疫细胞浸润。原代细胞培养结果表明,与对照滑膜成纤维细胞相比,MoM滑膜成纤维细胞的凋亡率从14降低到6%。此外,MoM患者的滑膜成纤维细胞保留了较高的收缩力,并增强了基质收缩对趋化性的反应性。如通过牵引力显微镜和原子力显微镜测得的,收缩力增加60%和更高的细胞刚度(MoM为3.3 kPa,对照组为2.18 kPa)观察到,它们在单个细胞水平上的机械性能有所提高。此外,MoM患者的成纤维细胞通过分泌单核细胞趋化蛋白1(MCP-1,CCL2)促进免疫细胞侵袭并诱导单核细胞分化,这也可能与滑膜巨噬细胞的过量积聚有关。体内暴露于释放CoCr磨损碎片的MoM THA植入物的滑膜成纤维细胞表现出显着的表型改变和功能变化。这些发现揭示了CoCr合金的出乎意料的效果,并证明了滑膜成纤维细胞在MoM THA引起的不良组织反应中的重要作用。通过牵引力显微镜和原子力显微镜测量,对照中为18 kPa。此外,MoM患者的成纤维细胞通过分泌单核细胞趋化蛋白1(MCP-1,CCL2)促进免疫细胞侵袭并诱导单核细胞分化,这也可能与滑膜巨噬细胞的过量积聚有关。体内暴露于释放CoCr磨损碎片的MoM THA植入物的滑膜成纤维细胞表现出显着的表型改变和功能变化。这些发现揭示了CoCr合金的出乎意料的效果,并证明了滑膜成纤维细胞在MoM THA引起的不良组织反应中的重要作用。通过牵引力显微镜和原子力显微镜测量,对照中为18 kPa。此外,MoM患者的成纤维细胞通过分泌单核细胞趋化蛋白1(MCP-1,CCL2)促进免疫细胞侵袭并诱导单核细胞分化,这也可能与滑膜巨噬细胞的过量积聚有关。体内暴露于释放CoCr磨损碎片的MoM THA植入物的滑膜成纤维细胞表现出显着的表型改变和功能改变。这些发现揭示了CoCr合金的出乎意料的效果,并证明了滑膜成纤维细胞在MoM THA引起的不良组织反应中的重要作用。MoM患者的成纤维细胞通过分泌单核细胞趋化蛋白1(MCP-1,CCL2)促进免疫细胞侵袭并诱导单核细胞分化,这也可能与滑膜巨噬细胞的过度积累有关。体内暴露于释放CoCr磨损碎片的MoM THA植入物的滑膜成纤维细胞表现出显着的表型改变和功能变化。这些发现揭示了CoCr合金的出乎意料的效果,并证明了滑膜成纤维细胞在MoM THA引起的不良组织反应中的重要作用。MoM患者的成纤维细胞通过分泌单核细胞趋化蛋白1(MCP-1,CCL2)促进免疫细胞侵袭并诱导单核细胞分化,这也可能与滑膜巨噬细胞的过度积累有关。体内暴露于释放CoCr磨损碎片的MoM THA植入物的滑膜成纤维细胞表现出显着的表型改变和功能改变。这些发现揭示了CoCr合金的出乎意料的效果,并证明了滑膜成纤维细胞在MoM THA引起的不良组织反应中的重要作用。体内暴露于释放CoCr磨损碎片的MoM THA植入物的滑膜成纤维细胞表现出显着的表型改变和功能改变。这些发现揭示了CoCr合金的出乎意料的效果,并证明了滑膜成纤维细胞在MoM THA引起的不良组织反应中的重要作用。体内暴露于释放CoCr磨损碎片的MoM THA植入物的滑膜成纤维细胞表现出显着的表型改变和功能改变。这些发现揭示了CoCr合金的出乎意料的效果,并证明了滑膜成纤维细胞在MoM THA引起的不良组织反应中的重要作用。
更新日期:2020-08-27
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