Aloe-Emodin Attenuates Cisplatin-Induced Ferroptotic Osteogenic Impairment in Bone Marrow Stromal Cells Through a YAP1-Dependent Mechanism
- 1Department of Orthopedics, Affiliated Yongchuan Hospital of Chongqing Medical University, Chongqing, 402160, People’s Republic of China
- 2Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China
- 3Laboratory of Skeletal Development and Regeneration, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, People’s Republic of China
Abstract
Background: Chemotherapy-induced bone loss (CIBL) is an important complication of anticancer treatment and is partly attributed to impaired osteogenic differentiation of bone marrow stromal/mesenchymal cells (BMSCs). Aloe-emodin (AE), a natural anthraquinone compound, has shown tissue-protective and anti-ferroptotic activities in chemotherapy-related organ injury. Its role in cisplatin (CDDP)-induced osteogenic impairment remains unclear.
Purpose: To investigate whether ferroptosis contributes to CDDP-induced osteogenic suppression in BMSCs and whether AE protects against this process through a Yes-associated protein 1 (YAP1)-dependent mechanism.
Methods: The anti-tumor effective concentration of CDDP was determined in 143B osteosarcoma cells. ST2 cells and primary mouse and human BMSCs were used to establish an in vitro model of CDDP-induced osteogenic impairment. Ferroptosis-related changes were assessed by Fe2⁺ accumulation, reactive oxygen species (ROS)/lipid peroxidation (LPO), and expression of related markers. Osteogenic differentiation was evaluated by alkaline phosphatase (AP) staining and osteogenic gene expression. RNA-seq, pharmacological inhibition, and Yap1 knockdown were used for mechanistic analysis.
Results: CDDP concentrations that inhibited 143B cells also induced ferroptosis in ST2 cells, characterized by Fe2⁺ accumulation, increased ROS and LPO, decreased glutathione peroxidase 4 (GPX4), and impaired osteogenic differentiation. Ferrostatin-1 (Fer-1) alleviated ferroptotic stress and restored osteogenesis. Under co-treatment conditions, AE reduced Fe2⁺ overload, ROS and LPO, restored anti-ferroptotic defenses, and improved osteogenic differentiation in ST2 cells as well as in primary mouse and human BMSCs. AE did not protect 143B cells from CDDP cytotoxicity, but further enhanced CDDP-mediated growth inhibition. Mechanistically, CDDP suppressed YAP1 expression and nuclear localization, whereas AE restored YAP1 activity. Verteporfin and Yap1 knockdown abolished AE-mediated protection.
Conclusion: AE protects BMSCs from CDDP-induced ferroptotic osteogenic impairment through a YAP1-dependent mechanism without compromising the anti-osteosarcoma effect of CDDP in vitro.
Related
- Central relaxin-3/RXFP3 signaling potently drives orexigenic behaviors and attenuates cisplatin-induced anorexia and body weight loss
- Docosahexaenoic acid attenuates cisplatin nephrotoxicity by restoring mitophagy
- Cycloastragenol Attenuates Cisplatin-Induced Ovarian Toxicity in Rats: Associations With TERT Expression, Apoptotic Balance, and FOXO3a-mTOR-Related Signaling.
- Inter-individual variation in cisplatin-induced liver injury is associated with hepatic platinum accumulation and GSH/GST-dependent defense in male mice
- Vitamin D3 Attenuates Delirium-Like Cognitive Impairment in a Postoperative Mouse Model
BibTeX
@article{hong2026aloeemodin,
title = {{Aloe-Emodin Attenuates Cisplatin-Induced Ferroptotic Osteogenic Impairment in Bone Marrow Stromal Cells Through a YAP1-Dependent Mechanism}},
author = {Xiang Hong and Yufei Shao and Qing Sun and Jing Zhou and Mengfan Yang and Haoyang Zhao and Xun Tang and Xing Liu and Xiaolin Tu and Yujiao Liu and Gaohai Shao},
journal = {Drug Design, Development and Therapy},
year = {2026},
month = oct,
doi = {10.2147/dddt.s639514},
url = {https://doi.org/10.2147/dddt.s639514},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Aloe-Emodin Attenuates Cisplatin-Induced Ferroptotic Osteogenic Impairment in Bone Marrow Stromal Cells Through a YAP1-Dependent Mechanism
AU - Xiang Hong
AU - Yufei Shao
AU - Qing Sun
AU - Jing Zhou
AU - Mengfan Yang
AU - Haoyang Zhao
AU - Xun Tang
AU - Xing Liu
AU - Xiaolin Tu
AU - Yujiao Liu
AU - Gaohai Shao
PY - 2026
DA - 2026/10/30
JO - Drug Design, Development and Therapy
DO - 10.2147/dddt.s639514
UR - https://doi.org/10.2147/dddt.s639514
AB - Background: Chemotherapy-induced bone loss (CIBL) is an important complication of anticancer treatment and is partly attributed to impaired osteogenic differentiation of bone marrow stromal/mesenchymal cells (BMSCs). Aloe-emodin (AE), a natural anthraquinone compound, has shown tissue-protective and anti-ferroptotic activities in chemotherapy-related organ injury. Its role in cisplatin (CDDP)-induced osteogenic impairment remains unclear. Purpose: To investigate whether ferroptosis contributes to CDDP-induced osteogenic suppression in BMSCs and whether AE protects against this process through a Yes-associated protein 1 (YAP1)-dependent mechanism. Methods: The anti-tumor effective concentration of CDDP was determined in 143B osteosarcoma cells. ST2 cells and primary mouse and human BMSCs were used to establish an in vitro model of CDDP-induced osteogenic impairment. Ferroptosis-related changes were assessed by Fe2⁺ accumulation, reactive oxygen species (ROS)/lipid peroxidation (LPO), and expression of related markers. Osteogenic differentiation was evaluated by alkaline phosphatase (AP) staining and osteogenic gene expression. RNA-seq, pharmacological inhibition, and Yap1 knockdown were used for mechanistic analysis. Results: CDDP concentrations that inhibited 143B cells also induced ferroptosis in ST2 cells, characterized by Fe2⁺ accumulation, increased ROS and LPO, decreased glutathione peroxidase 4 (GPX4), and impaired osteogenic differentiation. Ferrostatin-1 (Fer-1) alleviated ferroptotic stress and restored osteogenesis. Under co-treatment conditions, AE reduced Fe2⁺ overload, ROS and LPO, restored anti-ferroptotic defenses, and improved osteogenic differentiation in ST2 cells as well as in primary mouse and human BMSCs. AE did not protect 143B cells from CDDP cytotoxicity, but further enhanced CDDP-mediated growth inhibition. Mechanistically, CDDP suppressed YAP1 expression and nuclear localization, whereas AE restored YAP1 activity. Verteporfin and Yap1 knockdown abolished AE-mediated protection. Conclusion: AE protects BMSCs from CDDP-induced ferroptotic osteogenic impairment through a YAP1-dependent mechanism without compromising the anti-osteosarcoma effect of CDDP in vitro.
SN - 1177-8881
ER -