Elevated suppressor of cytokine signaling-1 (SOCS-1): A mechanism for dysregulated osteoclastogenesis in HIV transgenic rats

Mark K. Lafferty, Lori Fantry, Joseph Bryant, Odell Jones, Dima Hammoud, M. Neale Weitzmann, George K. Lewis, Alfredo Garzino-Demo, William Reid

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)81-89
Number of pages9
JournalPathogens and Disease
Volume71
Issue number1
DOIs
StatePublished - Jun 2014

Keywords

  • HIV-1
  • Osteoclast
  • Osteoporosis
  • SOCS-1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology and Microbiology(all)
  • Microbiology (medical)
  • Infectious Diseases

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