Massively HIV-1-infected macrophages exhibit a severely hampered ability to differentiate into osteoclasts

Abstract

IntroductionOsteoclasts 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.MethodsPrimary 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.ResultsRapid, 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.ConclusionsThe 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.

The abortive SARS‐CoV‐2 infection of osteoclast precursors promotes their differentiation into osteoclasts

“…Human monocytes were isolated from the blood of anonymous healthy donors and differentiated as MDMs, as described previously. 16 Briefly, monocytes were seeded on slides in 24-well plates at a density of 5 × 10 5 cells/mL in RPMI medium (Gibco) supplemented with 10% heat-inactivated fetal bovine serum (FBS) (Sigma-Aldrich), 2 mM of L-glutamine (Gibco), 1 mM of sodium pyruvate (Gibco), penicillin-streptomycin (Sigma-Aldrich), and M-CSF (10 ng/mL) (StemCell Technologies) for 6 days. Then, mature OC were obtained from cultured MDM (osteoclast precursors) in alpha minimum essential medium (α-MEM) (Gibco) supplemented with 10% FBS, 2 mM of L-glutamine (Gibco), 1 mM of sodium pyruvate (Gibco), and penicillin-streptomycin (α-MEM complete medium), M-CSF (10 ng/mL), and RANKL (30 ng/mL) (StemCell Technologies) for 9 days (mature osteoclast).…”

“…In the case of HIV infection, bone resorption is promoted, with the extent influenced by the infection load. 15,16 On the other hand, Zika virus infection impedes bone remodeling in OC. 17 Research utilizing animal models suggests that SARS-CoV-2 affects bone metabolism both during acute infection and in the postrecovery phases.…”