Activation of synovial fibroblasts from patients at revision of their metal-on-metal total hip arthroplasty

Abstract

Background: 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. Results: 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.

ABT-263 Reduces Hypertrophic Scars by Targeting Apoptosis of Myofibroblasts

“…Evasion of apoptosis by myofibroblasts is one of the underlying mechanisms of various types of fibrotic disease ( Teofoli et al, 1999 ; Thannickal and Horowitz, 2006 ; Iqubal et al, 2020 ; Xu et al, 2020 ). Apoptosis is a physiological process in which cells are genetically programmed to self-destruct, including the intrinsic and extrinsic pathways.…”

Chromium Oxide Nanoparticle Impaired Osteogenesis and Cellular Response to Mechanical Stimulus

“…Following exposures, cell culture supernatants were harvested and analysed as previously depicted. 22 Five replicates of each exposure were tested with the assay repeated in three separate experiments.…”

Label-free detection of uptake, accumulation, and translocation of diesel exhaust particles in ex vivo perfused human placenta

“…This is likely due to (i) the direct contact between this epithelial barrier layer and the maternal blood and (ii) the layer’s syncytial nature (fusion of multiple cells without cell boundaries), which largely restricts paracellular transport. Accumulation of carbon particles in the syncytiotrophoblast may interfere with its many essential functions for maternal–fetal health, and therefore deserves increasing attention (as reviewed in [ 13 ]).…”

“…Recently, gestational air pollution has been linked with shorter newborn telomere length, a biomolecular marker in the core axis of aging, both in the placenta and cord blood [ 11 ]. Observed adverse effects could be caused by three major pathways: (i) the placental translocation of particles provoking direct fetotoxic effects, and/or (ii) the indirect maternal mediated effects caused by the accumulation of particles in maternal tissues causing maternal organ dysfunction or release of inflammatory mediators and soluble signaling factors that can reach the placenta and fetus and possibly induce toxic effects and/or (iii) the indirect placental mediated effects caused by the accumulation of particles in placental tissues disrupting essential barrier and transport functions or inducing the release of secondary mediators that indirectly interfere with fetal development [ 12 , 13 ]. In this regard, Bové et al recently detected black carbon (BC) particles, a constituent of combustion-derived particulate matter, in the placental tissue of pregnant women in function of ambient exposure levels [ 14 ].…”

“…Gestational DEP exposure resulted in reduced placental function (i.e., decreased placental efficiency, placental blood flow, and fetal vessel volume) and intra-uterine fetal growth retardation (accompanied with reduced insulin-like growth factor 1 fetal plasma levels) [ 23 ], as well as altered-olfactory based behavior in pups [ 24 ]. The underlying mechanisms are not fully understood and may include both direct (e.g., toxicity to fetal tissues from translocated particles) and indirect (e.g., inflammation or disturbed hormone secretion in maternal or placental tissue) effects [ 13 ]. In general, exposure of pregnant animal models can provide valuable insights into the biodistribution of substances or particles in a living organism, including potential placental transfer towards the fetus.…”