Figure 2.

S. aureus internalization into osteoblasts. Two entry mechanisms are depicted. One is mediated by fibronectin, which forms a bridge between staphylococcal FnBP adhesin and osteoblast α₁β₅ integrin. This interaction promotes expression of Tumor Necrosis Factor-Related Apoptosis Inducing Ligand (TRAIL), which induces caspase 8 activation and the consequent osteoblast apoptosis. The other way is mediated by the interaction of Staphylococcal protein A (SpA) and Tumor Necrosis Factor Receptor 1 (TNFR-1) on the osteoblast surface. This interaction promotes the expression of the Receptor Activator of NF Kappa B Ligand (RANKL), a key cytokine in promoting osteoclastogenesis. Bone destruction results from the apoptotic death of osteoblasts and from the activation of osteoclasts. Other, cytokines released by internalized osteoblasts recruit monocytes/macrophages and induce their differentiation into osteoclasts, thus corroborating osteoclastogenesis. Also depicted are bacteria nestled in the bone canaliculi and dormant bacteria within biofilm.