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Iron Overload Induces Oxidative Stress, Cell Cycle Arrest and Apoptosis in Chondrocytes
Clinical and experimental evidence point to the presence of considerable links between arthropathy, osteoarthritis (OA) in particular, and iron overload possibly due to oxidative stress and tissue damage. However, the specific cellular targets of iron overload-related oxidative stress in OA remain a...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8894434/ https://www.ncbi.nlm.nih.gov/pubmed/35252185 http://dx.doi.org/10.3389/fcell.2022.821014 |
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author | Karim, Asima Bajbouj, Khuloud Shafarin, Jasmin Qaisar, Rizwan Hall, Andrew C. Hamad, Mawieh |
author_facet | Karim, Asima Bajbouj, Khuloud Shafarin, Jasmin Qaisar, Rizwan Hall, Andrew C. Hamad, Mawieh |
author_sort | Karim, Asima |
collection | PubMed |
description | Clinical and experimental evidence point to the presence of considerable links between arthropathy, osteoarthritis (OA) in particular, and iron overload possibly due to oxidative stress and tissue damage. However, the specific cellular targets of iron overload-related oxidative stress in OA remain ambiguous. We examined the effects of iron overload on chondrocyte health using the C-20/A4 chondrocyte cell line. Cells were treated with increasing concentrations of ferric ammonium citrate (FAC) to mimic iron overload in vitro. Treated cells were assessed for cell viability, cycling, apoptosis, collagen II synthesis, and oxidative stress along with cellular iron content and the expression of key iron regulatory genes. FAC treatment resulted in an increase in ferritin expression and a significant decrease in the expression of hepcidin, ferroportin, transferrin receptors 1 (TfR1) and TfR2. Increased labile iron content was also evident, especially in cells treated with high FAC at 24 h. High doses of FAC treatment also induced higher levels of reactive oxygen species, reduced collagen II production, disrupted cell cycle and higher cell death as compared with untreated controls. In conclusion, findings presented here demonstrate that iron overload disrupts cellular iron homeostasis, which compromises the functional integrity of chondrocytes and leads to oxidative stress and apoptosis. |
format | Online Article Text |
id | pubmed-8894434 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88944342022-03-05 Iron Overload Induces Oxidative Stress, Cell Cycle Arrest and Apoptosis in Chondrocytes Karim, Asima Bajbouj, Khuloud Shafarin, Jasmin Qaisar, Rizwan Hall, Andrew C. Hamad, Mawieh Front Cell Dev Biol Cell and Developmental Biology Clinical and experimental evidence point to the presence of considerable links between arthropathy, osteoarthritis (OA) in particular, and iron overload possibly due to oxidative stress and tissue damage. However, the specific cellular targets of iron overload-related oxidative stress in OA remain ambiguous. We examined the effects of iron overload on chondrocyte health using the C-20/A4 chondrocyte cell line. Cells were treated with increasing concentrations of ferric ammonium citrate (FAC) to mimic iron overload in vitro. Treated cells were assessed for cell viability, cycling, apoptosis, collagen II synthesis, and oxidative stress along with cellular iron content and the expression of key iron regulatory genes. FAC treatment resulted in an increase in ferritin expression and a significant decrease in the expression of hepcidin, ferroportin, transferrin receptors 1 (TfR1) and TfR2. Increased labile iron content was also evident, especially in cells treated with high FAC at 24 h. High doses of FAC treatment also induced higher levels of reactive oxygen species, reduced collagen II production, disrupted cell cycle and higher cell death as compared with untreated controls. In conclusion, findings presented here demonstrate that iron overload disrupts cellular iron homeostasis, which compromises the functional integrity of chondrocytes and leads to oxidative stress and apoptosis. Frontiers Media S.A. 2022-02-18 /pmc/articles/PMC8894434/ /pubmed/35252185 http://dx.doi.org/10.3389/fcell.2022.821014 Text en Copyright © 2022 Karim, Bajbouj, Shafarin, Qaisar, Hall and Hamad. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Karim, Asima Bajbouj, Khuloud Shafarin, Jasmin Qaisar, Rizwan Hall, Andrew C. Hamad, Mawieh Iron Overload Induces Oxidative Stress, Cell Cycle Arrest and Apoptosis in Chondrocytes |
title | Iron Overload Induces Oxidative Stress, Cell Cycle Arrest and Apoptosis in Chondrocytes |
title_full | Iron Overload Induces Oxidative Stress, Cell Cycle Arrest and Apoptosis in Chondrocytes |
title_fullStr | Iron Overload Induces Oxidative Stress, Cell Cycle Arrest and Apoptosis in Chondrocytes |
title_full_unstemmed | Iron Overload Induces Oxidative Stress, Cell Cycle Arrest and Apoptosis in Chondrocytes |
title_short | Iron Overload Induces Oxidative Stress, Cell Cycle Arrest and Apoptosis in Chondrocytes |
title_sort | iron overload induces oxidative stress, cell cycle arrest and apoptosis in chondrocytes |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8894434/ https://www.ncbi.nlm.nih.gov/pubmed/35252185 http://dx.doi.org/10.3389/fcell.2022.821014 |
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