Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Mascarau, Rémi, Bertrand, Florent, Labrousse, Arnaud, Gennero, Isabelle, Poincloux, Renaud, Maridonneau-Parini, Isabelle, Raynaud-Messina, Brigitte, Vérollet, Christel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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
_version_ 1783537961180069888
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
work_keys_str_mv AT mascarauremi hiv1infectedhumanmacrophagesbysecretingranklcontributetoenhancedosteoclastrecruitment
AT bertrandflorent hiv1infectedhumanmacrophagesbysecretingranklcontributetoenhancedosteoclastrecruitment
AT labroussearnaud hiv1infectedhumanmacrophagesbysecretingranklcontributetoenhancedosteoclastrecruitment
AT genneroisabelle hiv1infectedhumanmacrophagesbysecretingranklcontributetoenhancedosteoclastrecruitment
AT poinclouxrenaud hiv1infectedhumanmacrophagesbysecretingranklcontributetoenhancedosteoclastrecruitment
AT maridonneaupariniisabelle hiv1infectedhumanmacrophagesbysecretingranklcontributetoenhancedosteoclastrecruitment
AT raynaudmessinabrigitte hiv1infectedhumanmacrophagesbysecretingranklcontributetoenhancedosteoclastrecruitment
AT verolletchristel hiv1infectedhumanmacrophagesbysecretingranklcontributetoenhancedosteoclastrecruitment