PTGS2 Silencing Inhibits Ferroptosis in Staphylococcus Aureus-induced Osteomyelitis By Blocking the IL-17A Signaling Pathway

Osteomyelitis caused by Staphylococcus aureus (S. aureus) infection is an inflammatory bone disease characterized by continuous bone destruction, which is difficult to treat. This research aimed to explore the molecular mechanisms of S. aureus-induced osteomyelitis. Using the GSE166522 and GSE227521 datasets, hub differentially expressed genes (DEGs) were screened by bioinformatics analysis. Hub gene expression levels were validated in S. aureus-induced mouse models. An inhibitor of PTGS2, etoricoxib, was used to assess the role of PTGS2 in the osteomyelitis mouse model. PTGS2 was silenced in an LPS-induced MC3T3-E1 cell model to study its effect on cell function. Six hub genes were screened, including ARG1, TIMP1, NOS2, PTGS2, SOCS3, and IL1B, highly expressed in the S. aureus-induced osteomyelitis model. Etoricoxib treatment attenuated the inflammatory infiltration of tibial tissue in mice with osteomyelitis. In vivo and in vitro, etoricoxib treatment and PTGS2 silencing reduced inflammatory factor (TNF-α, IL-1β, and IL-6) levels. PTGS2 silencing promoted LPS-induced MC3T3-E1 cell viability and inhibited apoptosis and ferroptosis. GPX4 and SLC7A11 protein levels were significantly increased after PTGS2 silencing. Mechanistically, IL-17A intervention significantly counteracted the impact of PTGS2 silencing on cell behaviors and secukinumab combined with PTGS2 silencing more effectively suppressed inflammation and ferroptosis, indicating that PTGS2 impeded the osteomyelitis progression by inhibiting the IL-17A pathway. Silencing PTGS2 reduces ferroptosis in S. aureus-induced osteomyelitis by obstructing the IL-17A pathway, which suggests a new approach for the treatment of osteomyelitis.