2. Academic Validation
  3. Bisphenol A exacerbates osteoblast ferroptosis via the p53/SLC7A11 axis: A novel mechanistic insight into environmental osteoporosis pathogenesis

Bisphenol A exacerbates osteoblast ferroptosis via the p53/SLC7A11 axis: A novel mechanistic insight into environmental osteoporosis pathogenesis

  • Ecotoxicol Environ Saf. 2025 Dec 13:309:119560. doi: 10.1016/j.ecoenv.2025.119560.
Weilun Zhao 1,  Xiaoming Peng 2,  Fayun Yang 3,  Yi Zhang 3,  Yuhang Wei 4,  Jianhua Huang 5,  Yilin Teng 3,  Baicheng Wan 3,  Gaofeng Zeng 6,  Shaohui Zong 7
Affiliations

Affiliations

  • 1 Department of Spine Osteopathia, The First Affiliated Hospital, Guangxi Medical University, Nanning 530000, China; Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning, China.
  • 2 Department of Spine Osteopathia, The First Affiliated Hospital, Guangxi Medical University, Nanning 530000, China; Department of Joint and Bone Diseases, Yuebei People's Hospital, Affiliated Hospital of Shantou University, Shaoguan 512000, China.
  • 3 Department of Spine Osteopathia, The First Affiliated Hospital, Guangxi Medical University, Nanning 530000, China.
  • 4 School of Public Health of Guangxi Medical University, Nanning, Guangxi, China.
  • 5 Wuming Hospital of Guangxi Medical University, Nanning 530000, China.
  • 6 School of Public Health of Guangxi Medical University, Nanning, Guangxi, China. Electronic address: [email protected].
  • 7 Department of Spine Osteopathia, The First Affiliated Hospital, Guangxi Medical University, Nanning 530000, China; Wuming Hospital of Guangxi Medical University, Nanning 530000, China. Electronic address: [email protected].
PMID: 41391364 DOI: 10.1016/j.ecoenv.2025.119560
Abstract

Bisphenol A (BPA) is a ubiquitous industrial pollutant, but its role in osteoporosis is not fully understood. This paper combines network toxicology, experimental, and molecular docking validation to illuminate how BPA disrupts bone metabolism. We identified 142 BPA related proteins linked to osteoporosis, narrowing to 6 core targets by protein-protein interaction analysis. Molecular docking confirmed strong binding of BPA to these targets. In vitro and in vivo experiments showed that BPA suppressed osteoblast viability and differentiation. Quantitative analyses further revealed strong negative correlations between BPA exposure levels on key osteogenic parameters, such as reduced Alkaline Phosphatase activity, downregulation of OPN, OCN, and RUNX2. Mechanically, BPA induces osteoblastic Ferroptosis by increasing the accumulation of p53, which enhances degradation of SLC7A11, which is a critical Ferroptosis protein. Notably, we show a novel post-translational regulatory mechanism where p53 regulates SLC7A11 protein stability, rather than transcription. We show a novel toxicological mechanism by which BPA exacerbates osteoporosis and provide a new target for potential therapeutic interventions focused on protein stability and post-translational modifications.

Keywords

BPA; P53; SLC7A11; ferroptosis; toxicology.

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