Staphylococcus aureusandSalmonella entericaSerovar Dublin Induce Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Expression by Normal Mouse and Human Osteoblasts

Abstract

Staphylococcus aureus and Salmonella enterica serovar Dublin invade osteoblasts and are causative agents of human bone disease. In the present study, we examined the ability of S. aureus and Salmonella serovar Dublin to induce the production of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by normal osteoblasts. Normal mouse and human osteoblasts were cocultured with S. aureus or Salmonella serovar Dublin at different multiplicities of infection. Following initial incubation and examination of TRAIL expression, extracellular bacteria were killed by the addition of media containing the antibiotic gentamicin. Lysates and conditioned media from osteoblast cultures were then collected at various times following invasion and analyzed. The results demonstrated that S. aureus and Salmonella serovar Dublin are potent inducers of TRAIL expression by osteoblasts. Mouse and human TRAIL mRNA expression was induced by bacterial infection and demonstrated a dose-dependent response. Analysis of kinetics suggested that TRAIL mRNA was induced within 30 min after exposure to bacteria and that its level of expression remained relatively constant over the time period examined. mRNA molecules encoding TRAIL receptors were constitutively expressed by osteoblasts. Furthermore, TRAIL protein was detected as early as 45 min and up to 24 h following infection. The quantity of TRAIL protein produced also increased in a dose-dependent manner. Collectively, these findings suggest a mechanism whereby bacterial pathogens mediate bone destruction via osteoblast apoptosis.

Inflammatory T cells rapidly induce differentiation of human bone marrow stromal cells into mature osteoblasts

“…In the presence of TRAIL, OPG loses its ability to inhibit RANKL induced osteoclastogenesis ]. Our studies showing that human osteoblasts express TRAIL confirm that of others [Alexander et al, 2001;Evdokiou et al, 2002]. And most importantly, TRAIL induces apoptosis in human osteogenic sarcoma cells, but not in normal human osteoblasts, despite their expression of the receptors for TRAIL [Evdokiou et al, 2002].…”

Heterotopic Ossification Following Traumatic and Combat-Related Amputations

“…Finally, infection has been proven to be a detriment to bone formation and fracture-healing in both basic-science and clinical studies and appears to favor osteoblast apoptosis and osteoclastogenesis through a complex inflammatory cascade [28][29][30][31] . However, in our series, all cultures of specimens that were obtained at the time of heterotopic ossification excision were positive.…”

Staphylococcus aureus - induced tumor necrosis factor - related apoptosis - inducing ligand expression mediates apoptosis and caspase-8 activation in infected osteoblasts

“…Other studies have demonstrated induction of TRAIL by Theiler's murine encephalomyelitis virus (TMEV) in M1-D cells (a myelomonocytic precursor cell line) [37], reovirus infection in fibroblasts [38], HIV-1 infection in CD4 + T cells [39], and adenovirus in 239T cells [40]. The demonstration of caspase-8 involvement in S. aureus -induced apoptosis is complemented by a recent report from our laboratory that S. aureus induces expression of TRAIL by infected osteoblasts [41]. We reported that S. aureus strongly induces TRAIL expression by both normal mouse and normal human osteoblasts, while mRNAs encoding the death-domain-containing TRAIL receptors are constitutively expressed in the same cells.…”