Aloe emodin alleviates ferroptosis mediated inhibition of cisplatin-induced osteogenic differentiation of BMSCS through Hippo-YAP1 signaling pathway

This study demonstrates that aloe-emodin (AE) rescues CDDP-impaired osteogenic differentiation in ST2 BMSCs by suppressing ferroptosis (reducing lipid peroxidation and iron accumulation), while concurrently enhancing death in 143B osteosarcoma cells. Mechanistically, AE activated the Hippo-YAP1 signaling pathway, increasing YAP1 protein levels and nuclear translocation.

Bioinformatics and functional validation (YAP1 inhibitor Verteporfin and overexpression) confirmed that AE's anti-ferroptotic and pro-osteogenic effects critically depend on Hippo-YAP1 activation. Verteporfin abolished AE's protection, directly linking YAP1 to the reversal of CDDP-induced damage. This dual action of AE—bone protection via Hippo-YAP1-mediated ferroptosis inhibition in BMSCs and tumor suppression in osteosarcoma—highlights its therapeutic potential against chemotherapy-induced bone loss, revealing a novel strategy targeting the Hippo-YAP1-ferroptosis axis.