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HIV-1-Infected Human Macrophages, by Secreting RANK-L, Contribute to Enhanced Osteoclast Recruitment
HIV-1 infection is frequently associated with low bone density, which can progress to osteoporosis leading to a high risk of fractures. Only a few mechanisms have been proposed to explain the enhanced osteolysis in the context of HIV-1 infection. As macrophages are involved in bone homeostasis and a...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246503/ https://www.ncbi.nlm.nih.gov/pubmed/32365752 http://dx.doi.org/10.3390/ijms21093154 |
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author | Mascarau, Rémi Bertrand, Florent Labrousse, Arnaud Gennero, Isabelle Poincloux, Renaud Maridonneau-Parini, Isabelle Raynaud-Messina, Brigitte Vérollet, Christel |
author_facet | Mascarau, Rémi Bertrand, Florent Labrousse, Arnaud Gennero, Isabelle Poincloux, Renaud Maridonneau-Parini, Isabelle Raynaud-Messina, Brigitte Vérollet, Christel |
author_sort | Mascarau, Rémi |
collection | PubMed |
description | HIV-1 infection is frequently associated with low bone density, which can progress to osteoporosis leading to a high risk of fractures. Only a few mechanisms have been proposed to explain the enhanced osteolysis in the context of HIV-1 infection. As macrophages are involved in bone homeostasis and are critical host cells for HIV-1, we asked whether HIV-1-infected macrophages could participate in bone degradation. Upon infection, human macrophages acquired some osteoclast features: they became multinucleated, upregulated the osteoclast markers RhoE and β3 integrin, and organized their podosomes as ring superstructures resembling osteoclast sealing zones. However, HIV-1-infected macrophages were not fully differentiated in osteoclasts as they did not upregulate NFATc-1 transcription factor and were unable to degrade bone. Investigating whether infected macrophages participate indirectly to virus-induced osteolysis, we showed that they produce RANK-L, the key osteoclastogenic cytokine. RANK-L secreted by HIV-1-infected macrophages was not sufficient to stimulate multinucleation, but promoted the protease-dependent migration of osteoclast precursors. In conclusion, we propose that, by stimulating RANK-L secretion, HIV-1-infected macrophages contribute to create a microenvironment that favors the recruitment of osteoclasts, participating in bone disorders observed in HIV-1 infected patients. |
format | Online Article Text |
id | pubmed-7246503 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72465032020-06-11 HIV-1-Infected Human Macrophages, by Secreting RANK-L, Contribute to Enhanced Osteoclast Recruitment Mascarau, Rémi Bertrand, Florent Labrousse, Arnaud Gennero, Isabelle Poincloux, Renaud Maridonneau-Parini, Isabelle Raynaud-Messina, Brigitte Vérollet, Christel Int J Mol Sci Article HIV-1 infection is frequently associated with low bone density, which can progress to osteoporosis leading to a high risk of fractures. Only a few mechanisms have been proposed to explain the enhanced osteolysis in the context of HIV-1 infection. As macrophages are involved in bone homeostasis and are critical host cells for HIV-1, we asked whether HIV-1-infected macrophages could participate in bone degradation. Upon infection, human macrophages acquired some osteoclast features: they became multinucleated, upregulated the osteoclast markers RhoE and β3 integrin, and organized their podosomes as ring superstructures resembling osteoclast sealing zones. However, HIV-1-infected macrophages were not fully differentiated in osteoclasts as they did not upregulate NFATc-1 transcription factor and were unable to degrade bone. Investigating whether infected macrophages participate indirectly to virus-induced osteolysis, we showed that they produce RANK-L, the key osteoclastogenic cytokine. RANK-L secreted by HIV-1-infected macrophages was not sufficient to stimulate multinucleation, but promoted the protease-dependent migration of osteoclast precursors. In conclusion, we propose that, by stimulating RANK-L secretion, HIV-1-infected macrophages contribute to create a microenvironment that favors the recruitment of osteoclasts, participating in bone disorders observed in HIV-1 infected patients. MDPI 2020-04-30 /pmc/articles/PMC7246503/ /pubmed/32365752 http://dx.doi.org/10.3390/ijms21093154 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mascarau, Rémi Bertrand, Florent Labrousse, Arnaud Gennero, Isabelle Poincloux, Renaud Maridonneau-Parini, Isabelle Raynaud-Messina, Brigitte Vérollet, Christel HIV-1-Infected Human Macrophages, by Secreting RANK-L, Contribute to Enhanced Osteoclast Recruitment |
title | HIV-1-Infected Human Macrophages, by Secreting RANK-L, Contribute to Enhanced Osteoclast Recruitment |
title_full | HIV-1-Infected Human Macrophages, by Secreting RANK-L, Contribute to Enhanced Osteoclast Recruitment |
title_fullStr | HIV-1-Infected Human Macrophages, by Secreting RANK-L, Contribute to Enhanced Osteoclast Recruitment |
title_full_unstemmed | HIV-1-Infected Human Macrophages, by Secreting RANK-L, Contribute to Enhanced Osteoclast Recruitment |
title_short | HIV-1-Infected Human Macrophages, by Secreting RANK-L, Contribute to Enhanced Osteoclast Recruitment |
title_sort | hiv-1-infected human macrophages, by secreting rank-l, contribute to enhanced osteoclast recruitment |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246503/ https://www.ncbi.nlm.nih.gov/pubmed/32365752 http://dx.doi.org/10.3390/ijms21093154 |
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