Schisandrol B inhibits osteoclastogenesis and mitigates estrogen deficiency-induced bone loss by targeting TRAF6-NOX1 pathway.

BACKGROUND

An enhanced number of osteoclasts accompanied by abnormal bone resorption activity are major contributing factors to systemic bone diseases such as osteoporosis. Directing the suppression of osteoclastogenesis is a crucial approach to combating osteoporosis. Nevertheless, the effects of Schisandrol B (SolB) from Schisandra chinensis lignan on osteoclasts and osteoporosis remain unclear.

PURPOSE: This study aims to uncover how SolB inhibits osteoclasts and prevents estrogen deficiency-induced osteoporosis.

METHODS

The impacts of SolB osteoclast production, F-actin ring formation, bone resorption, intracellular ROS, and antioxidant enzymes were examined in vitro. Transcriptome analysis was used to analyze the effects of SolB on RANKL-mediated signaling pathways. Molecular docking, dynamics, and surface plasmon resonance (SPR) were used for binding confirmation of SolB and the target proteins. The OVX model was used to examine SolB's protective effect on bone mass in mice.

RESULTS

In vitro experiments demonstrated that SolB inhibited osteoclast production and bone resorption by enhancing antioxidant enzymes to reduce intracellular ROS and decrease intracellular Ca2+ and NFATc1 expression. SolB suppressed TRAF6-NF-κB and MAPK signaling pathways activation stimulated by RANKL. SPR results revealed that SolB could bind to TRAF6 and NOX1. SolB effectively protected against bone loss in OVX mice by lowering NOX1 expression and enhancing antioxidant enzyme expression.

CONCLUSION

Our results suggest that SolB is a potentially effective drug for preventing and treating postmenopausal osteoporosis.