Sesquiterpene Lactone Parthenolide Blocks Lipopolysaccharide‐Induced Osteolysis Through the Suppression of NF‐κB Activity

摘要: UNLABELLED Effective treatment for bacteria-induced bone lytic diseases is not yet available. In this study, we showed that PAR, an NF-kappaB inhibitor found in medicinal herbs, can block LPS-induced osteolysis. PAR does by inhibiting osteoclastogenesis and resorption promoting apoptosis of osteoclasts through the suppression activity. INTRODUCTION Osteolysis induced chronic gram-negative bacterial infection underlies many such as osteomyelitis, septic arthritis, periodontitis. Drugs inhibit lipopolysaccharide (LPS)-induced osteolysis are critically needed prevention destruction infective diseases. investigated effect parthenolide (PAR) on vivo studied its role osteoclastogenesis, resorption, apoptosis, MATERIALS AND METHODS The mouse calvarium model was used to examine vivo. RANKL-induced osteoclast differentiation from RAW264.7 cells assays were assess vitro. Assays activation, p65 translocation, IkappaB-alpha degradation determine mechanism action their precursors. Flow cytometry confocal microscopic analysis cell apoptosis. Semiquantitative RT-PCR performed gene expression RANK TRAF6. RESULTS We (0.5 1 mg/kg), injected simultaneously with LPS (25 mg/kg) or 3 days later, blocked model. vitro studies low concentrations ( 5 microM) triggered apoptotic death precursor a dose-dependent manner. Furthermore, inhibited both mature precursors time- addition, activation osteoclastogenic factors RANKL, interleukin (IL)-1beta, TNF-alpha varying degrees reduced CONCLUSION pathway known mediate survival. These findings indicate blocks activity suggest it might have therapeutic value destruction.