Abstract
Accelerated bone loss leading to osteopenia, osteoporosis, and bone fracture is a major health problem that is increasingly common in human immunodeficiency virus (HIV)-infected patients. The underlying pathogenesis is unclear but occurs in both treatment naïve and individuals receiving antiretroviral therapies. We developed an HIV-1 transgenic rat that exhibits many key features of HIV disease including HIV-1-induced changes in bone mineral density (BMD). A key determinant in the rate of bone loss is the differentiation of osteoclasts, the cells responsible for bone resorption. We found HIV-1 transgenic osteoclast precursors (OCP) express higher levels of suppressor of cytokine signaling-1 (SOCS-1) and TNF receptor-associated factor 6 (TRAF6) and are resistant to interferon-gamma (IFN-γ) mediated suppression of osteoclast differentiation. Our data suggest that dysregulated SOCS-1 expression by HIV-1 transgenic OCP promotes osteoclastogenesis leading to the accelerated bone loss observed in this animal model. We propose that elevated SOCS-1 expression in OCP antagonizes the inhibitory effects of IFN-γ and enhances receptor activator of NF-kB ligand (RANKL) signaling that drives osteoclast differentiation and activation. Understanding the molecular mechanisms of HIV-associated BMD changes has the potential to detect and treat bone metabolism disturbances early and improve the quality of life in patients.
Original language | English (US) |
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Pages (from-to) | 81-89 |
Number of pages | 9 |
Journal | Pathogens and Disease |
Volume | 71 |
Issue number | 1 |
DOIs | |
State | Published - Jun 2014 |
Externally published | Yes |
Keywords
- HIV-1
- Osteoclast
- Osteoporosis
- SOCS-1
ASJC Scopus subject areas
- Immunology and Allergy
- General Immunology and Microbiology
- Microbiology (medical)
- Infectious Diseases