Causative agents of osteomyelitis induce death domain-containing TNF-related apoptosis-inducing ligand receptor expression on osteoblasts.
Bacteria and their products are potent inducers of bone destruction. While inflammatory damage during conditions such as osteomyelitis is associated with increased formation and activity of bone-resorbing osteoclasts, it is likely that bone loss also results from the elimination of the cells responsible for matrix deposition. Consistent with this notion, we have previously demonstrated that bone-forming osteoblasts undergo apoptosis following bacterial challenge and that this cell death is due, at least in part, to the actions of TNF-related apoptosis-inducing ligand (TRAIL). In the present study, we demonstrate that primary osteoblasts constitutively express death domain containing TRAIL receptors. Importantly, we show that cell surface expression of the death-inducing receptors DR4 and DR5 on murine and human osteoblasts is restricted to cells infected with the principle causative agents of osteomyelitis, Staphylococcus aureus and Salmonella. In addition, we show that the robust constitutive production by osteoblasts of the decoy TRAIL receptor, OPG, is inhibited following bacterial infection. Finally, we report that while exogenous administration of TRAIL fails to activate apoptosis signaling pathways in uninfected osteoblasts, acute bacterial exposure sensitizes these cells to this ligand. Based upon these findings we suggest a model in which bacterially challenged osteoblasts express TRAIL while concomitantly decreasing the production of the decoy receptor OPG and upregulating cell surface death receptor expression. Such an increase in TRAIL bioavailability and induced sensitivity of infected osteoblasts to this ligand would result in apoptotic cell death of this bone-forming population, providing an additional mechanism underlying inflammatory bone loss during diseases such as osteomyelitis.
Department of Biology, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.
Amy B
AB
Young
Ian D
ID
Cooley
Vinita S
VS
Chauhan
Ian
I
Marriott
D000818:Animals; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism*; D010019:Osteomyelitis / Q000382:microbiology*; D016133:Polymerase Chain Reaction; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand