Isobavachin inhibits osteoclastogenesis in inflammatory osteolysis loss by modulating the ROS-mediated Nrf2/HO-1 signaling pathway

OBJECTIVES: Isobavachin (Ibv), a monomeric compound derived from a traditional Chinese herb, demonstrates a range of biological activities. However, the precise effects of Ibv on inflammatory osteolysis remain inadequately understood. The present study seeks to elucidate the mechanisms underlying Ibv's inhibitory effects on osteoclasts (OCs) differentiation and inflammatory osteolysis. METHODS: The CCK-8 assay assessed cell viability with Ibv treatment, while tartrate acid phosphatase staining, podosome belt staining, and bone resorption assays evaluated Ibv's impact on OCs differentiation and OCs function. PCR and Western blot analyses were conducted to assess the expression of key genes and proteins. The model of inflammatory osteolysis induced by lipopolysaccharide was utilized. KEY FINDINGS: Ibv significantly inhibits OCs differentiation besides suppressing lipopolysaccharide-induced inflammatory osteolysis. micro-computed tomography analysis demonstrated that Ibv treatment markedly improved bone microarchitecture. Ibv hinders OCs formation and activation by downregulating TRAF6 and enhancing NRF2 expression, lowering ROS levels in OCs. This modulation further impeded the downstream NF-κB and MAPK pathways, ultimately suppressing bone resorption. CONCLUSIONS: The present study highlights Ibv's capacity to restrain OCs differentiation and inflammatory osteolysis, imposing its probability as a therapeutic agent for conditions. The proposed mechanism of action encompasses the regulation of the ROS/NF-κB and MAPK pathways, establishing a conceptual basis for the advancement of Ibv in therapeutic applications.