mRNA Transcriptome Analysis of Bone in a Mouse Model of Implant-Associated Staphylococcus aureus Osteomyelitis.

To investigate the molecular pathogenesis of bone with osteomyelitis, we developed implant-associated osteomyelitis (IAOM) models in mice. An orthopedic stainless pin was surgically placed in the right femoral midshaft of mice, followed by an inoculation of Staphylococcus aureus into the medullary cavity. Typical characteristics of IAOM, like periosteal reaction and intraosseous abscess, occurred by day 14 postinfection. By day 28 postinfection, necrotic abscess, sequestrum formation, and deformity of the whole femur were observed. Transcriptional analysis identified 101 and 1,702 differentially expressed genes (DEGs) between groups by days 3 and 14 postinfection, respectively. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed the enrichment of pathways in response to the bacterium, receptor-ligand activity, and chemokine signaling by day 3 postinfection. However, by day 14 postinfection, the enrichment switched to angiogenesis, positive regulation of cell motility and migration, skeletal system development, and cytokine-cytokine receptor interaction. Furthermore, protein-protein interaction network analysis identified 4 cytokines (interleukin 6 [IL-6], Cxcl10, gamma interferon [IFN-γ], and Cxcl9) associated with IAOM at an early stage of infection. Overall, as the pathological changes in this mouse model were consistent with those in human IAOM, our model may be used to investigate the mechanism and treatment of IAOM. Furthermore, the data for transcriptome sequencing and bioinformatic analysis will be an important resource for dissecting the molecular pathogenesis of bone with IAOM.