UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Molecular analysis of HIF activation as a potential biomarker for adverse reaction to metal debris (ARMD) in tissue and blood samples

Nyga, A; Hart, A; Tetley, TD; (2019) Molecular analysis of HIF activation as a potential biomarker for adverse reaction to metal debris (ARMD) in tissue and blood samples. Journal of Biomedical Materials Research - Part B Applied Biomaterials , 107 (5) pp. 1352-1362. 10.1002/jbm.b.34227. Green open access

[thumbnail of JBMB_uncorrectedproofs.pdf]
Preview
Text
JBMB_uncorrectedproofs.pdf - Accepted Version

Download (1MB) | Preview

Abstract

We aimed to find a biomarker for patients with adverse reaction to metal debris (ARMD) due to a metal-on-metal (MoM) hip implant. First, we compared molecular markers of hypoxia-inducible factor (HIF) pathway activation (BNIP3, GLUT1, HO1, VEGF, and HIF1A) and inflammatory response (IL1B and COX2) in tissue from patients undergoing revision of MoM hip implant with tissue from patients undergoing primary hip replacement (PHR). Second, we compared blood levels of the above molecular markers and additional inflammatory markers: TNFA, IL18, CASPASE1, NFKB or IKB, and TLR1–4 mRNA in patients with non-failed MoM hips. We report the presence of increased expression of HIF-target genes in the periprosthetic tissue in MoM patients when compared to the PHR group. This suggests HIF pathway activation due to MoM debris and the potential of using HIF targets as a predictor of failure. Analysis of blood samples from nonoverlapping, nonfailed, MoM group showed significantly higher expression of COX2 mRNA and significant correlations between HIF1A and GLUT1 mRNA expressions, and between HIF1A mRNA and selection of inflammatory genes, including IL18, IKB, TLR1, and TLR4. HIF pathway activation in the periprosthetic tissue biopsies of patients with hip replacements may represent the first biomarker to identify early ARMD. Further studies investigating blood biomarkers could also prove beneficial in detecting ARMD that could lead to an early intervention and improved patient outcome after hip revision surgery. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res B Part B: Appl Biomater, 2018.

Type: Article
Title: Molecular analysis of HIF activation as a potential biomarker for adverse reaction to metal debris (ARMD) in tissue and blood samples
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/jbm.b.34227
Publisher version: https://doi.org/10.1002/jbm.b.34227
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: MoM, cobalt‐chromium, inflammation, hypoxia‐inducible factor pathway
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Ortho and MSK Science
URI: https://discovery.ucl.ac.uk/id/eprint/10070352
Downloads since deposit
200Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item