Zingerone attenuates Ti particle-induced inflammatory osteolysis by suppressing the NF-κB signaling pathway in osteoclasts.

Abstract

Aseptic loosening caused by inflammatory osteolysis is one of the most frequent and serious long-term complications after total joint arthroplasty (TJA). Development of a new therapeutic drug is required due to the lack of effective therapy and serious adverse effects. This study aimed to explore the pharmacological properties of zingerone (ZO) in attenuating osteoclast-mediated periprosthetic osteolysis and how ZO modulates osteoclastogenesis. The nontoxic concentration of ZO was clarified by the CCK-8 method. Then, we explored the efficacy of ZO on suppressing osteoclast differentiation, F-actin ring formation, bone resorption, and NF-κB luciferase activity in vitro as well as osteoprotection in vivo. Polymerase chain reaction and western blotting were applied to detect the underlying mechanisms involved in osteoclastogenesis. ZO showed an obvious inhibitory effect on osteoclastogenesis and bone resorption in a dose-dependent manner by mainly suppressing the activation of NF-κB signaling pathways. Furthermore, ZO administration successfully attenuated titanium (Ti) particle-stimulated periprosthetic osteolysis and osteoporosis by regulating osteoclast formation. Our findings demonstrated the pharmacological properties of ZO in inhibiting osteoclast formation and function by downregulation of NF-κB signaling activation. As a result, these findings could be expected to provide a novel reagent for regulating inflammatory osteolysis caused by prosthetic loosening.