PD0325901 Alleviates Thrombin-Inhibited Osteogenic Differentiation Through an IL-1β-Activated Feedback Loop between MEK-Erk1/2 and NF-κB Signal Pathways: Insights from Bioinformatics and Experimental Verification

Thrombin transcriptionally induces inflammatory genes and suppresses osteogenic markers via RNA-seq identified pathways. The MEK inhibitor PD0325901 (PD03) is identified to be a key modulator targeting the IL-1β-MMP-9 axis. Our finding highlights that PD03 inhibits thrombin-induced suppression of osteoblast differentiation through repressing IL-1β-mediated MEK-Erk1/2 and NF-κB feedback loop and restoring osteogenic gene expression.