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Updated: Jul 24, 2025
Isolation, Transfection, and Culture of Primary Human Monocytes
Published on: December 16, 2019
Massively HIV-1-infected macrophages exhibit a severely hampered ability to differentiate into osteoclasts
Franco A Sviercz1, Patricio Jarmoluk1, Cintia G Cevallos1
1Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS); Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Insights
HIV infection severely impairs osteoclast differentiation, affecting bone resorption and density. This study reveals how HIV impacts key cellular processes, crucial for understanding bone health in HIV-positive individuals.
Area of Science:
- Immunology
- Cell Biology
- Bone Biology
Background:
- Osteoclasts are vital for bone resorption; their dysfunction impacts bone density.
- Individuals with HIV are at risk for altered bone health.
- Understanding HIV's effect on osteoclast differentiation is critical.
Purpose of the Study:
- To investigate the impact of HIV infection on osteoclast differentiation.
- To assess HIV's effects on cellular adhesion, cathepsin K expression, and resorptive activity.
- To examine the influence of HIV on cytokine production, co-receptor expression, and transcriptional regulation in osteoclastogenesis.
Main Methods:
- Primary human monocyte-derived macrophages were used as osteoclast precursors.
- Macrophages were infected with HIV, analyzing inoculum size and viral replication kinetics.
- Osteoclastogenesis was evaluated by measuring cellular adhesion, cathepsin K expression, resorptive activity, cytokine production (IL-1β, RANK-L), co-receptor expression (CCR5, CD9, CD81), and key transcription factors (RANK, NFATc1, DC-STAMP).
Main Results:
- Rapid, massive HIV infection severely impaired osteoclast differentiation, compromising cellular adhesion, cathepsin K expression, and resorptive activity.
- HIV infection led to earlier IL-1β production with RANK-L, suppressing osteoclast formation.
- High HIV inoculum increased CCR5, CD9, and CD81 expression, correlating with deficient osteoclastogenesis and altered transcription of RANK, NFATc1, and DC-STAMP.
Conclusions:
- HIV infection's impact on osteoclast precursors depends on inoculum size and viral replication kinetics.
- These findings highlight the importance of understanding HIV's mechanisms on bone cells.
- This research is crucial for developing strategies to prevent and treat bone disorders in individuals with HIV.
Introduction:
Osteoclasts play a crucial role in bone resorption, and impairment of their differentiation can have significant implications for bone density, especially in individuals with HIV who may be at risk of altered bone health. The present study aimed to investigate the effects of HIV infection on osteoclast differentiation using primary human monocyte-derived macrophages as precursors. The study focused on assessing the impact of HIV infection on cellular adhesion, cathepsin K expression, resorptive activity, cytokine production, expression of co-receptors, and transcriptional regulation of key factors involved in osteoclastogenesis.
Methods:
Primary human monocyte-derived macrophages were utilized as precursors for osteoclast differentiation. These precursors were infected with HIV, and the effects of different inoculum sizes and kinetics of viral replication were analyzed. Subsequently, osteoclastogenesis was evaluated by measuring cellular adhesion, cathepsin K expression, and resorptive activity. Furthermore, cytokine production was assessed by monitoring the production of IL-1β, RANK-L, and osteoclasts. The expression levels of co-receptors CCR5, CD9, and CD81 were measured before and after infection with HIV. The transcriptional levels of key factors for osteoclastogenesis (RANK, NFATc1, and DC-STAMP) were examined following HIV infection.
Results:
Rapid, massive, and productive HIV infection severely impaired osteoclast differentiation, leading to compromised cellular adhesion, cathepsin K expression, and resorptive activity. HIV infection resulted in an earlier production of IL-1β concurrent with RANK-L, thereby suppressing osteoclast production. Infection with a high inoculum of HIV increased the expression of the co-receptor CCR5, as well as the tetraspanins CD9 and CD81, which correlated with deficient osteoclastogenesis. Massive HIV infection of osteoclast precursors affected the transcriptional levels of key factors involved in osteoclastogenesis, including RANK, NFATc1, and DC-STAMP.
Conclusions:
The effects of HIV infection on osteoclast precursors were found to be dependent on the size of the inoculum and the kinetics of viral replication. These findings underscore the importance of understanding the underlying mechanisms to develop novel strategies for the prevention and treatment of bone disorders in individuals with HIV.
