Activation of synovial fibroblasts from patients at revision of their metal-on-metal total hip arthroplasty
- PDF / 1,990,368 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 26 Downloads / 159 Views
RESEARCH
Open Access
Activation of synovial fibroblasts from patients at revision of their metal-on-metal total hip arthroplasty Jing Xu1,2†, Junyao Yang2,3†, Jian Chen4, Xiaoli Zhang2, Yuanhao Wu2, Alister Hart5, Agata Nyga6,7* Julia C. Shelton2*
and
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. (Continued on next page)
* Correspondence: [email protected]; [email protected] † Jing Xu and Junyao Yang contributed equally to this work. 6 Research Department of Surgical Biotechnology, Division of Surgery and Interventional Sciences, University College London, London NW3 2QG, UK 2 Institute of Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, London, UK Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the origi
Data Loading...
