HIV-1 triggers apoptosis in primary osteoblasts and HOBIT cells through TNFalpha activation.
Several HIV-1 infected patients show bone loss and osteopenia/osteoporosis during the course of disease. The mechanisms underlying this degenerative process are largely unsettled and it has not been determined yet whether bone dysfunction is linked to HIV-1-mediated direct and/or indirect effects on osteoblasts/osteoclasts cross-talk regulation. This study investigated the effects of HIV-1(IIIb) and HIV-1(ADA) strains on osteoblasts using the osteoblast-derived cell line (HOBIT) and primary human osteoblasts as cellular models. The challenge of these cell cultures by both HIV-1 strains triggered a significant apoptosis activation unrelated to viral infection, since proviral HIV-1 DNA and supernatant HIV-1 RNA were not detected by real time PCR or b-DNA assays respectively. Under the experimental conditions, even heat-inactivated HIV-1 or cross-linked recombinant gp120 treatment of HOBIT and osteoblasts induced programmed cell death, suggesting that apoptosis is regulated by the interaction between HIV-1 gp120 and cell membrane. The analysis of cell culture supernatants showed a significant up-regulation of TNFalpha, a pleiotropic protein considered an apoptosis inducer in the osteoblast model. In fact, pretreatment of HOBIT and osteoblast cell cultures with anti-TNFalpha polyclonal antibody tackled effectively HIV-1 related induction of cell apoptosis. As a whole, these results indicate that HIV-1 may impair bone mass structure homeostasis by TNFalpha regulated osteoblast apoptosis.
Gibellini
Davide
D
Department of Clinical and Experimental Medicine, Microbiology Section, University of Bologna, Bologna, Italy. davide.gibellini@unibo.it
De Crignis
Elisa
E
Ponti
Cristina
C
Cimatti
Laura
L
Borderi
Marco
M
Tschon
Matilde
M
Giardino
Roberto
R
Re
Maria Carla
MC
D017209:Apoptosis; D002460:Cell Line; D002478:Cells, Cultured; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D005786:Gene Expression Regulation; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000150:complications / Q000473:pathology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D010006:Osteoblasts / Q000821:virology*; D011533:Proviruses / Q000235:genetics / Q000302:isolation & purification; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D004279:DNA, Viral; D015699:HIV Envelope Protein gp120; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; C514793:gp120 protein, Human immunodeficiency virus 1