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...
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| Format: | Article |
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MDPI AG
2020-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/9/3154 |
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| author | Rémi Mascarau Florent Bertrand Arnaud Labrousse Isabelle Gennero Renaud Poincloux Isabelle Maridonneau-Parini Brigitte Raynaud-Messina Christel Vérollet |
| author_facet | Rémi Mascarau Florent Bertrand Arnaud Labrousse Isabelle Gennero Renaud Poincloux Isabelle Maridonneau-Parini Brigitte Raynaud-Messina Christel Vérollet |
| author_sort | Rémi Mascarau |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T20:08:29Z |
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| id | doaj.art-7efe14c2875747be8461243a0e306b01 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T20:08:29Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7efe14c2875747be8461243a0e306b012023-11-19T23:05:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01219315410.3390/ijms21093154HIV-1-Infected Human Macrophages, by Secreting RANK-L, Contribute to Enhanced Osteoclast RecruitmentRémi Mascarau0Florent Bertrand1Arnaud Labrousse2Isabelle Gennero3Renaud Poincloux4Isabelle Maridonneau-Parini5Brigitte Raynaud-Messina6Christel Vérollet7Institut de Pharmacologie et Biologie Structurale, Université de Toulouse, CNRS UMR 5089, Université Toulouse III Paul Sabatier, CEDEX 04, 31077 Toulouse, FranceInstitut de Pharmacologie et Biologie Structurale, Université de Toulouse, CNRS UMR 5089, Université Toulouse III Paul Sabatier, CEDEX 04, 31077 Toulouse, FranceInstitut de Pharmacologie et Biologie Structurale, Université de Toulouse, CNRS UMR 5089, Université Toulouse III Paul Sabatier, CEDEX 04, 31077 Toulouse, FranceCentre de Physiopathologie de Toulouse-Purpan, INSERM-CNRS UMR 1043, Université Toulouse III Paul Sabatier, 31024 Toulouse, FranceInstitut de Pharmacologie et Biologie Structurale, Université de Toulouse, CNRS UMR 5089, Université Toulouse III Paul Sabatier, CEDEX 04, 31077 Toulouse, FranceInstitut de Pharmacologie et Biologie Structurale, Université de Toulouse, CNRS UMR 5089, Université Toulouse III Paul Sabatier, CEDEX 04, 31077 Toulouse, FranceInstitut de Pharmacologie et Biologie Structurale, Université de Toulouse, CNRS UMR 5089, Université Toulouse III Paul Sabatier, CEDEX 04, 31077 Toulouse, FranceInstitut de Pharmacologie et Biologie Structurale, Université de Toulouse, CNRS UMR 5089, Université Toulouse III Paul Sabatier, CEDEX 04, 31077 Toulouse, FranceHIV-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.https://www.mdpi.com/1422-0067/21/9/3154HIV-1macrophagesosteoclastsbone defectsRANK-Lcell migration |
| spellingShingle | Rémi Mascarau Florent Bertrand Arnaud Labrousse Isabelle Gennero Renaud Poincloux Isabelle Maridonneau-Parini Brigitte Raynaud-Messina Christel Vérollet HIV-1-Infected Human Macrophages, by Secreting RANK-L, Contribute to Enhanced Osteoclast Recruitment International Journal of Molecular Sciences HIV-1 macrophages osteoclasts bone defects RANK-L cell migration |
| 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 | HIV-1 macrophages osteoclasts bone defects RANK-L cell migration |
| url | https://www.mdpi.com/1422-0067/21/9/3154 |
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