Osteoblasts Express the Inflammatory Cytokine Interleukin-6 in a Murine Model of Staphylococcus aureus Osteomyelitis and Infected Human Bone Tissue

Abstract

Staphylococcus aureus is the single most common cause of osteomyelitis in humans. Incidences of osteomyelitis caused by S. aureus have increased dramatically in recent years, in part due to the appearance of community-acquired antibiotic resistant strains. Therefore, understanding the pathogenesis of this organism has become imperative. Recently, we have described the surprising ability of bone-forming osteoblasts to secrete a number of important immune mediators when exposed to S. aureus in vitro. In the present study, we provide the first evidence for the in vivo production of such molecules by osteoblasts during bacterial infection of bone. These studies demonstrate the expression of the key inflammatory cytokine interleukin-6 by osteoblasts in organ cultures of neonatal mouse calvaria, and in vivo using a mouse model that closely resembles the pathology of trauma-induced staphylococcal osteomyelitis, as determined by confocal microscopic analysis. Importantly, we have established the clinical relevancy of these findings in infected human bone tissue from patients with S. aureus-associated osteomyelitis. As such, these studies demonstrate that bacterial challenge of osteoblasts during bone diseases, such as osteomyelitis, induces cells to produce inflammatory molecules that can direct appropriate host responses or contribute to progressive inflammatory damage.

Establishment of a Real-Time, Quantitative, and Reproducible Mouse Model of Staphylococcus Osteomyelitis Using Bioluminescence Imaging

“…Marriott et al (22) demonstrated that osteoblasts express IL-6 during bacterial bone infection in a mouse model and in human bone tissues. IL-6 (12, 17) and IL-1␤ (4,25), which are produced by stimulated monocytes/macrophages, stimulate osteoclasts and lead to bone resorption.…”

The Immunogenicity and Immunomodulatory Function of Osteogenic Cells Differentiated from Mesenchymal Stem Cells

“…Although the immunosuppressive function of DOC is promising, it cannot be ignored that DOC gradually expressed MHC class II and lost their suppressive activity in vivo. It is reported that POC expressed all immune surface markers which can elicit an immune response, and they are able to act as APCs (42)(43)(44)(45)(46). Hence, it is predicted that DOC in vivo are going the way their progeny normally does.…”

Quantitative mouse model of implant‐associated osteomyelitis and the kinetics of microbial growth, osteolysis, and humoral immunity

“…4 To date, much of our knowledge of the pathogenesis of OM comes from animal models, 5 which have existed in chicken, 6 rat, 7,8 guinea pig, 9 rabbit, 10 dog, 11 sheep, 12 goat, 13 and most recently mouse. 14 While these models have been used to confirm the importance of bacterial adhesions identified from in vitro assays, [15][16][17] none of them contain quantitative endpoints that can determine bacterial load or growth in vivo. Thus, they are of limited value for assessing drug effects, bacterial mutants, and the role of host factors during the establishment of chronic OM.…”