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

► HIV-1 Tat enhances osteoclast differentiation. ► HIV-1 Tat up-regulates c-fos expression during osteoclast differentiation. ► HIV-1 Tat affects bone homeostasis. Impaired osteoblast/osteoclast cross-talk and bone structure homeostasis resulting in osteopenia/osteoporosis are often observed in HIV...

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Veröffentlicht in:Biochemical and biophysical research communications 2010-10, Vol.401 (3), p.429-434
Hauptverfasser: Gibellini, Davide, De Crignis, Elisa, Ponti, Cristina, Borderi, Marco, Clò, Alberto, Miserocchi, Anna, Viale, Pierluigi, Carla Re, Maria
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Sprache:eng
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Zusammenfassung:► HIV-1 Tat enhances osteoclast differentiation. ► HIV-1 Tat up-regulates c-fos expression during osteoclast differentiation. ► HIV-1 Tat affects bone homeostasis. 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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2010.09.071