Myh7 regulates SDRC protein and biofilm formation to alleviate osteomyelitis induced by Staphylococcus aureus

Abstract

SDRC is implicated in the pathogenesis of Staphylococcus aureus osteomyelitis. However, the precise mechanism by which SDRC contributes to the progression of this infection remains unclear. To explore SDRC’s role in osteomyelitis, experiments were conducted on mouse models infected with Staphylococcus aureus strains containing either the wild type SDRC sequence or a knockout (KO-SDRC) sequence. Levels of inflammatory factors like IL-6 and TNF-α were measured using Elisa. Furthermore, changes in osteogenic indicators such as ALP, OST, and Runx2 were detected using qPCR and Western blot analysis. Additionally, transcriptome sequencing was employed to gain deeper insights into the potential molecular mechanisms underlying SDRC’s promotion of Staphylococcus aureus-induced osteomyelitis. The study revealed that the ability of Staphylococcus aureus to form biofilms was significantly weakened in strains where the SDRC protein was knocked out. Moreover, mice infected with the KO-SDRC strain exhibited enhanced ossification processes. Transcriptome sequencing demonstrated significant overexpression of the Myh7 gene in the SDRC knockout osteomyelitis mouse. Subsequent knockout of the Myh7 gene led to notable reductions in mRNA and protein expressions of osteogenic indicators including Runx2, ALP, OSX, and Osteocalcin. Overall, these findings suggest that SDRC plays a crucial role in promoting the malignant progression of osteomyelitis caused by Staphylococcus aureus. Its main mechanism involves enhancing the formation of Staphylococcus aureus biofilms. Conversely, Myh7 may exert an inhibitory effect on the SDRC protein, reducing biofilm formation and mitigating the severity of osteomyelitis. These findings offer novel insights into potential therapeutic targets for the treatment of osteomyelitis.