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Effects of Metal Ion Exposure on Organ Systems

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 2584

Special Issue Editor


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Guest Editor
Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
Interests: joint replacement; epidemiology of implant–host interactions; genetics of musculoskeletal disease; disease biomarkers; metabolic bone disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

All metal-containing joint replacement prostheses release metal debris into the local and systemic tissue environments. This debris arises as a result of wear and corrosion at the prosthesis surfaces. Local adverse tissue responses to this released metal have resulted in a substantially higher prosthesis failure rate in prostheses using cobalt–chromium at the bearing surfaces and other modular interfaces. Case reports of severe systemic illness involving cardiac, neurological, and other distant organ systems have also been associated with excessive wear or corrosion of cobalt–chromium alloy-containing prostheses. Despite this burden of clinical disease associated with metal ion exposure, the magnitude of the underlying risk associated with metal-on-metal bearings and interfaces remains unclear and the relevant molecular pathways are poorly characterized.

This Special Issue of the International Journal of Molecular Sciences will focus on recent advances in our understanding of “Adverse Reactions to Metal Debris”, including new insights into the epidemiology as it relates to disease mechanisms, pathogenesis, and molecular biology of ARMD. The issue will include articles addressing both adverse responses at the local tissue level and those addressing the effects at distant organ sites. Topics will include those exploring the relationship between magnitude of exposure and disease burden, the spectrum of organ systems that may be implicated, toxicology, disease biomarkers, and the biological mechanisms that underpin the observed pathologies.

Prof. Dr. Mark Wilkinson
Guest Editor

Manuscript Submission Information

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Keywords

  • Cobalt
  • Chromium
  • Exposure
  • Adverse response to metal debris
  • Epidemiology
  • Pathogenesis
  • Biomarker
  • Toxicology

Published Papers (1 paper)

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Research

14 pages, 9882 KiB  
Article
Distinct Concentration-Dependent Molecular Pathways Regulate Bone Cell Responses to Cobalt and Chromium Exposure from Joint Replacement Prostheses
by Karan M. Shah, Mark J. Dunning, Alison Gartland and J. Mark Wilkinson
Int. J. Mol. Sci. 2021, 22(10), 5225; https://doi.org/10.3390/ijms22105225 - 14 May 2021
Cited by 4 | Viewed by 1895
Abstract
Systemic cobalt (Co) and chromium (Cr) concentrations may be elevated in patients with metal joint replacement prostheses. Several studies have highlighted the detrimental effects of this exposure on bone cells in vitro, but the underlying mechanisms remain unclear. In this study, we use [...] Read more.
Systemic cobalt (Co) and chromium (Cr) concentrations may be elevated in patients with metal joint replacement prostheses. Several studies have highlighted the detrimental effects of this exposure on bone cells in vitro, but the underlying mechanisms remain unclear. In this study, we use whole-genome microarrays to comprehensively assess gene expression in primary human osteoblasts, osteoclast precursors and mature resorbing osteoclasts following exposure to clinically relevant circulating versus local periprosthetic tissue concentrations of Co2+ and Cr3+ ions and CoCr nanoparticles. We also describe the gene expression response in osteoblasts on routinely used prosthesis surfaces in the presence of metal exposure. Our results suggest that systemic levels of metal exposure have no effect on osteoblasts, and primarily inhibit osteoclast differentiation and function via altering the focal adhesion and extracellular matrix interaction pathways. In contrast, periprosthetic levels of metal exposure inhibit both osteoblast and osteoclast activity by altering HIF-1α signaling and endocytic/cytoskeletal genes respectively, as well as increasing inflammatory signaling with mechanistic implications for adverse reactions to metal debris. Furthermore, we identify gene clusters and KEGG pathways for which the expression correlates with increasing Co2+:Cr3+ concentrations, and has the potential to serve as early markers of metal toxicity. Finally, our study provides a molecular basis for the improved clinical outcomes for hydroxyapatite-coated prostheses that elicit a pro-survival osteogenic gene signature compared to grit-blasted and plasma-sprayed titanium-coated surfaces in the presence of metal exposure. Full article
(This article belongs to the Special Issue Effects of Metal Ion Exposure on Organ Systems)
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