biostudies-literatureRamani HNIA NIH HHSNIH HHS481https://www.ebi.ac.uk/biostudies/studies/S-EPMC11987946biostudies-literatureUnknown14(7)People with HIV (PWH) have an increased risk of developing cardiovascular disease (CVD). Our recent data demonstrated that the multi-isoform proinflammatory cytokine IL-32 is upregulated in PWH and is associated with arterial stiffness and subclinical atherosclerosis. However, the mechanisms by which IL-32 contributes to the pathogenesis of these diseases remain unclear. Here, we show that while the less expressed IL-32α isoform induces the differentiation of human classical monocytes into the calcium-resorbing osteoclast cells, the dominantly expressed isoforms IL-32β and IL-32γ suppress this function through the inhibition of TGF-β and induce the differentiation of monocytes into the calcium-depositing osteocalcin+ osteoblasts. These results aligned with the increase in plasma levels of CellsOpposite Roles of IL-32α Versus IL-32β/γ Isoforms in Promoting Monocyte-Derived Osteoblast/Osteoclast Differentiation and Vascular Calcification in People with HIV.PMC119879462R01AG054324-08A1R01 AG054324Kizer JRSylla MThomas RJenabian MADurand MMartel-Laferriere VTremblay CLRamani HCloutier GChomont NChartrand-Lefebvre CBertrand FLanday ALPeet MMAncuta PFortin CCleret-Buhot ATrottier BHanna DBAllard LEl-Far MSadouni MBunet RRouty JPKaplan RCfalseOpposite Roles of IL-32α Versus IL-32β/γ Isoforms in Promoting Monocyte-Derived Osteoblast/Osteoclast Differentiation and Vascular Calcification in People with HIV.People with HIV (PWH) have an increased risk of developing cardiovascular disease (CVD). Our recent data demonstrated that the multi-isoform proinflammatory cytokine IL-32 is upregulated in PWH and is associated with arterial stiffness and subclinical atherosclerosis. However, the mechanisms by which IL-32 contributes to the pathogenesis of these diseases remain unclear. Here, we show that while the less expressed IL-32α isoform induces the differentiation of human classical monocytes into the calcium-resorbing osteoclast cells, the dominantly expressed isoforms IL-32β and IL-32γ suppress this function through the inhibition of TGF-β and induce the differentiation of monocytes into the calcium-depositing osteocalcin+ osteoblasts. These results aligned with the increase in plasma levels of 2025-01-01T00:00:00Z2025 Mar2025-07-06T03:05:40.974Z2025-07-06T03:05:40.974ZS-EPMC119879464021443510.3390/cells14070481