HIV-1-Infected Human Macrophages, by Secreting RANK-L, Contribute to Enhanced Osteoclast Recruitment

Autor: Brigitte Raynaud-Messina, Florent Bertrand, Isabelle Gennero, Christel Vérollet, Isabelle Maridonneau-Parini, Arnaud Labrousse, Renaud Poincloux, Rémi Mascarau
Přispěvatelé: Raynaud-Messina, Brigitte, Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Rok vydání: 2020
Předmět:
Osteolysis
cell migration
Podosome
[SDV]Life Sciences [q-bio]
medicine.medical_treatment
Fluorescent Antibody Technique
Gene Expression
HIV Infections
RANK-L
Giant Cells
lcsh:Chemistry
0302 clinical medicine
Cell Movement
lcsh:QH301-705.5
Cells
Cultured
ComputingMilieux_MISCELLANEOUS
Spectroscopy
0303 health sciences
Cell migration
General Medicine
macrophages
3. Good health
Computer Science Applications
[SDV] Life Sciences [q-bio]
medicine.anatomical_structure
Cytokine
030220 oncology & carcinogenesis
bone defects
Context (language use)
Biology
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
Multinucleate
Osteoclast
medicine
Humans
Secretion
Physical and Theoretical Chemistry
Molecular Biology
030304 developmental biology
RANK Ligand
Organic Chemistry
medicine.disease
osteoclasts
lcsh:Biology (General)
lcsh:QD1-999
HIV-1
Cancer research
Biomarkers
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, 2020, 21 (9), pp.3154. ⟨10.3390/ijms21093154⟩
International Journal of Molecular Sciences, Vol 21, Iss 3154, p 3154 (2020)
Volume 21
Issue 9
International Journal of Molecular Sciences, MDPI, 2020, 21 (9), pp.3154. ⟨10.3390/ijms21093154⟩
International Journal of Molecular Sciences, MDPI, 2020, 21 (9), ⟨10.3390/ijms21093154⟩
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms21093154
Popis: 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 &beta
3 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.
Databáze: OpenAIRE
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