Related Experiment Video
Updated: May 14, 2025
Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes
Published on: January 27, 2023
Opposite Roles of IL-32α Versus IL-32β/γ Isoforms in Promoting Monocyte-Derived Osteoblast/Osteoclast Differentiation
Hardik Ramani1,2, Aurélie Cleret-Buhot2,3, Mohamed Sylla2
1Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, QC H3C 3J7, Canada.
Insights
People with HIV (PWH) have higher cardiovascular disease (CVD) risk. Proinflammatory cytokine IL-32 influences immune cells, promoting vascular calcification and worsening CVD in PWH.
Area of Science:
- Immunology
- Cardiovascular Medicine
- Molecular Biology
Background:
- People with HIV (PWH) exhibit elevated cardiovascular disease (CVD) risk.
- The proinflammatory cytokine IL-32 is upregulated in PWH and linked to arterial stiffness and subclinical atherosclerosis.
- Mechanisms underlying IL-32's role in PWH CVD pathogenesis are not fully understood.
Purpose of the Study:
- To elucidate the mechanisms by which IL-32 contributes to CVD pathogenesis in PWH.
- To investigate the differential effects of IL-32 isoforms on monocyte differentiation.
- To correlate IL-32's effects with vascular calcification biomarkers in PWH.
Main Methods:
- Assessed the impact of IL-32 isoforms (IL-32α, IL-32β, IL-32γ) on human classical monocyte differentiation into osteoclasts and osteoblasts.
- Measured plasma levels of osteoprotegerin (OPG), a vascular calcification biomarker.
- Correlated OPG levels with subclinical coronary artery atherosclerosis and calcium scores in PWH.
Main Results:
- The less expressed IL-32α isoform promoted monocyte differentiation into osteoclasts.
- Dominantly expressed IL-32β and IL-32γ isoforms inhibited osteoclastogenesis and promoted osteoblast differentiation via TGF-β inhibition.
- Elevated plasma OPG levels were observed in PWH and associated with coronary artery calcification.
Conclusions:
- IL-32 isoforms differentially regulate monocyte differentiation, impacting vascular calcification.
- IL-32 promotes vascular calcification in PWH, contributing to their increased CVD risk.
- Targeting IL-32 may offer a novel therapeutic strategy for CVD in people with HIV.
Abstract:
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 osteoprotegerin, a biomarker of vascular calcification, and its association with the presence of coronary artery subclinical atherosclerosis and calcium score in PWH. These findings support a novel role for the proinflammatory cytokine IL-32 in the pathophysiology of CVD by increasing vascular calcification in PWH.
Related Concept Videos
01:24T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
01:31Osteoclasts in Bone Remodeling
01:01Regulation of Hematopoietic Stem Cells