Conclusions
Our results showed the potential of anti-oxidant compound schisandrin A in the treatment of osteoporosis, highlighting Nrf2 as a novel promising target in osteoclast-related disease.
Material and methods
Micro-CT was used to detect bone formation. The effects of Sch on receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced reactive oxygen species (ROS) were measured by dihydroethidium (DHE) staining in vivo and 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining in vitro. Immunofluorescence staining was used to detect the expression of Nrf2 in vivo. siRNA was used to evaluate the effect of Nrf2 in osteoclastogenesis.
Methods
Micro-CT was used to detect bone formation. The effects of Sch on receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced reactive oxygen species (ROS) were measured by dihydroethidium (DHE) staining in vivo and 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining in vitro. Immunofluorescence staining was used to detect the expression of Nrf2 in vivo. siRNA was used to evaluate the effect of Nrf2 in osteoclastogenesis.
Results
Sch suppresses RANKL-induced ROS production by regulating nuclear factor erythroid 2-related factor (Nrf2) in vitro and vivo. Mechanistically, Sch enhances the expression of Nrf2 by regulating the degradation of Nrf2. Further, Sch suppresses phosphorylation of P65 and its nuclear translocation, as well as the degradation of IκBα. Collectively, our findings reveal that Sch protects against OVX-induced bone loss by suppressing ROS via Nrf2. Conclusions: Our results showed the potential of anti-oxidant compound schisandrin A in the treatment of osteoporosis, highlighting Nrf2 as a novel promising target in osteoclast-related disease.