Opposite 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 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.
Authors
- Réjean Thomas (ORCID: https://orcid.org/0000-0002-9112-3561)
- Manel Sadouni (ORCID: https://orcid.org/0000-0003-4751-7675)
- Benoît Trottier (ORCID: https://orcid.org/0000-0002-9285-848X)
- Madéleine Durand (ORCID: https://orcid.org/0000-0002-9459-9549)
- Alan Landay (ORCID: https://orcid.org/0000-0001-9645-1356)
- Louise Allard (ORCID: https://orcid.org/0000-0002-8204-9056)
- Guy Cloutier (ORCID: https://orcid.org/0000-0002-4957-4844)
- Petronela Ancuța (ORCID: https://orcid.org/0000-0003-1922-5640)
- Claude Fortin (ORCID: https://orcid.org/0000-0001-9334-3093)
- Jean‐Pierre Routy (ORCID: https://orcid.org/0000-0001-9897-7589)
- Jorge R. Kizer (ORCID: https://orcid.org/0000-0001-9936-7803)
- Rémi Bunet
- Carl Chartrand‐Lefebvre (ORCID: https://orcid.org/0000-0002-2299-7855)
- Hardik Ramani
- Aurélie Cleret‐Buhot
- Valérie Martel‐Laferrière (ORCID: https://orcid.org/0000-0001-7973-8582)
- Cécile Tremblay (ORCID: https://orcid.org/0000-0002-3440-3436)
- Florent Bertrand (ORCID: https://orcid.org/0000-0003-4516-7587)
- Mohammad‐Ali Jenabian (ORCID: https://orcid.org/0000-0003-4321-9777)
- Matthew M. Peet (ORCID: https://orcid.org/0000-0001-9360-6738)
- Nicolas Chomont (ORCID: https://orcid.org/0000-0001-9747-5018)
- Robert C. Kaplan (ORCID: https://orcid.org/0000-0003-1571-4615)
- Mohamed Sylla
- Mohamed El‐Far (ORCID: https://orcid.org/0000-0002-6458-4207)
- David B. Hanna (ORCID: https://orcid.org/0000-0002-1985-9865)
Institutions
- Albert Einstein College of Medicine (US)
- San Francisco VA Medical Center (US)
- Université du Québec à Montréal (CA)
- University of California, San Francisco (US)
- McGill University Health Centre (CA)
- Fred Hutch Cancer Center (US)
- Centre Hospitalier de l’Université de Montréal (CA)
- Université de Montréal (CA)
- The University of Texas at Austin (US)
Publication Details
- Journal
- Cells
- Published
- 2025-03-22
- DOI
- https://doi.org/10.3390/cells14070481
- Citations
- 3
- Primary Topic
- Bone Metabolism and Diseases
- Type
- article
- Field-Weighted Citation Impact
- 2.42
Funders
- National Institutes of Health
- Canadian Institutes of Health Research