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Alteration of osteoclast activity in childhood cancer survivors: Role of iron and of CB2/TRPV1 receptors
Childhood cancer survivors (CCS) are predisposed to the onset of osteoporosis (OP). It is known that iron overload induces osteoclasts (OCs) overactivity and that the iron chelator Deferasirox (DFX) can counteract it. The Cannabinoid Receptor type 2 (CB2) and the transient receptor potential vanillo...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302719/ https://www.ncbi.nlm.nih.gov/pubmed/35862357 http://dx.doi.org/10.1371/journal.pone.0271730 |
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author | Rossi, Francesca Tortora, Chiara Di Martino, Martina Di Paola, Alessandra Di Pinto, Daniela Marrapodi, Maria Maddalena Argenziano, Maura Pota, Elvira |
author_facet | Rossi, Francesca Tortora, Chiara Di Martino, Martina Di Paola, Alessandra Di Pinto, Daniela Marrapodi, Maria Maddalena Argenziano, Maura Pota, Elvira |
author_sort | Rossi, Francesca |
collection | PubMed |
description | Childhood cancer survivors (CCS) are predisposed to the onset of osteoporosis (OP). It is known that iron overload induces osteoclasts (OCs) overactivity and that the iron chelator Deferasirox (DFX) can counteract it. The Cannabinoid Receptor type 2 (CB2) and the transient receptor potential vanilloid type-1 (TRPV1) are potential therapeutic targets for OP. In this study we isolated OCs from peripheral blood of 20 CCS and investigated osteoclast biomarkers expression and iron metabolism evaluating iron release by OCs and the expression of several molecules involved in its regulation. Moreover, we analyzed the effects of CB2 and TRPV1 stimulation in combination with DFX on osteoclast activity and iron metabolism. We observed, for the first time, an osteoclast hyperactivation in CCS suggesting a role for iron in its development. Moreover, we confirmed the well-known role of CB2 and TRPV1 receptors in bone metabolism, suggesting the receptors as possible key biomarkers of bone damage. Moreover, we demonstrated a promising synergism between pharmacological compounds, stimulating CB2 or inhibiting/desensitizing TRPV1 and DFX, in counteracting osteoclast overactivity in CCS to improve their quality of life. |
format | Online Article Text |
id | pubmed-9302719 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-93027192022-07-22 Alteration of osteoclast activity in childhood cancer survivors: Role of iron and of CB2/TRPV1 receptors Rossi, Francesca Tortora, Chiara Di Martino, Martina Di Paola, Alessandra Di Pinto, Daniela Marrapodi, Maria Maddalena Argenziano, Maura Pota, Elvira PLoS One Research Article Childhood cancer survivors (CCS) are predisposed to the onset of osteoporosis (OP). It is known that iron overload induces osteoclasts (OCs) overactivity and that the iron chelator Deferasirox (DFX) can counteract it. The Cannabinoid Receptor type 2 (CB2) and the transient receptor potential vanilloid type-1 (TRPV1) are potential therapeutic targets for OP. In this study we isolated OCs from peripheral blood of 20 CCS and investigated osteoclast biomarkers expression and iron metabolism evaluating iron release by OCs and the expression of several molecules involved in its regulation. Moreover, we analyzed the effects of CB2 and TRPV1 stimulation in combination with DFX on osteoclast activity and iron metabolism. We observed, for the first time, an osteoclast hyperactivation in CCS suggesting a role for iron in its development. Moreover, we confirmed the well-known role of CB2 and TRPV1 receptors in bone metabolism, suggesting the receptors as possible key biomarkers of bone damage. Moreover, we demonstrated a promising synergism between pharmacological compounds, stimulating CB2 or inhibiting/desensitizing TRPV1 and DFX, in counteracting osteoclast overactivity in CCS to improve their quality of life. Public Library of Science 2022-07-21 /pmc/articles/PMC9302719/ /pubmed/35862357 http://dx.doi.org/10.1371/journal.pone.0271730 Text en © 2022 Rossi et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Rossi, Francesca Tortora, Chiara Di Martino, Martina Di Paola, Alessandra Di Pinto, Daniela Marrapodi, Maria Maddalena Argenziano, Maura Pota, Elvira Alteration of osteoclast activity in childhood cancer survivors: Role of iron and of CB2/TRPV1 receptors |
title | Alteration of osteoclast activity in childhood cancer survivors: Role of iron and of CB2/TRPV1 receptors |
title_full | Alteration of osteoclast activity in childhood cancer survivors: Role of iron and of CB2/TRPV1 receptors |
title_fullStr | Alteration of osteoclast activity in childhood cancer survivors: Role of iron and of CB2/TRPV1 receptors |
title_full_unstemmed | Alteration of osteoclast activity in childhood cancer survivors: Role of iron and of CB2/TRPV1 receptors |
title_short | Alteration of osteoclast activity in childhood cancer survivors: Role of iron and of CB2/TRPV1 receptors |
title_sort | alteration of osteoclast activity in childhood cancer survivors: role of iron and of cb2/trpv1 receptors |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302719/ https://www.ncbi.nlm.nih.gov/pubmed/35862357 http://dx.doi.org/10.1371/journal.pone.0271730 |
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