HIV-1 Tat protein enhances RANKL/M-CSF-mediated osteoclast differentiation.
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.
Gibellini
Davide
D
Department of Haematology and Oncological Sciences, Microbiology Section, University of Bologna, Italy. davide.gibellini@unibo.it
De Crignis
Elisa
E
Ponti
Cristina
C
Borderi
Marco
M
Clò
Alberto
A
Miserocchi
Anna
A
Viale
Pierluigi
P
Re
Maria Carla
MC
D001851:Bone Diseases, Metabolic / Q000235:genetics / Q000821:virology*; D056657:Cathepsin K / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D005786:Gene Expression Regulation; D016762:Genes, fos; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D010010:Osteoclasts / Q000166:cytology*; D010024:Osteoporosis / Q000235:genetics / Q000821:virology*; D053245:RANK Ligand / Q000494:pharmacology; D018003:Receptors, Calcitonin / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000235:genetics; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
D053245:RANK Ligand; D018003:Receptors, Calcitonin; C505688:TNFSF11 protein, human; D018808:Transcription Factor AP-1; D054322:tat Gene Products, Human Immunodeficiency Virus; D016173:Macrophage Colony-Stimulating Factor; D056657:Cathepsin K