HIV-1 Tat protein enhances RANKL/M-CSF-mediated osteoclast differentiation

Biochem Biophys Res Commun. 2010 Oct 22;401(3):429-34. doi: 10.1016/j.bbrc.2010.09.071. Epub 2010 Sep 24.

Abstract

Impaired osteoblast/osteoclast cross-talk and bone structure homeostasis resulting in osteopenia/osteoporosis are often observed in HIV seropositive patients but the causal mechanisms remain unsettled. This study analyzed the biological effects of Tat on peripheral blood monocyte-derived osteoclast differentiation. Tat enhances osteoclast differentiation and activity induced by RANKL plus M-CSF treatment increasing both the mRNA expression of specific osteoclast differentiation markers, such as cathepsin K and calcitonin receptor, and TRAP expression and activity. These Tat-related biological effects may be related, at least in part, to the induction of c-fos expression and AP-1 activity. c-fos up-regulation was triggered by Tat when cell cultures were co-treated with RANKL/M-CSF and an analysis of c-fos promoter with c-fos deletion mutant constructs disclosed specific c-fos promoter domains targeted by Tat. Together, these results show that Tat may be considered a viral factor positively modulating the osteoclastogenesis and then bone resorption activity suggesting a pathogenetic role of this viral protein in the HIV-related osteopenia/osteoporosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Diseases, Metabolic / genetics
  • Bone Diseases, Metabolic / virology*
  • Cathepsin K / genetics
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics*
  • Gene Expression Regulation
  • Genes, fos
  • HIV-1 / metabolism*
  • Humans
  • Macrophage Colony-Stimulating Factor / pharmacology
  • Osteoclasts / cytology*
  • Osteoporosis / genetics
  • Osteoporosis / virology*
  • RANK Ligand / pharmacology
  • Receptors, Calcitonin / genetics
  • Transcription Factor AP-1 / genetics
  • tat Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • RANK Ligand
  • Receptors, Calcitonin
  • TNFSF11 protein, human
  • Transcription Factor AP-1
  • tat Gene Products, Human Immunodeficiency Virus
  • Macrophage Colony-Stimulating Factor
  • Cathepsin K