1. Academic Validation
  2. Chronic di(2-ethylhexyl) phthalate exposure at environmental-relevant doses induces osteoporosis by disturbing the differentiation of bone marrow mesenchymal stem cells

Chronic di(2-ethylhexyl) phthalate exposure at environmental-relevant doses induces osteoporosis by disturbing the differentiation of bone marrow mesenchymal stem cells

  • Sci Total Environ. 2024 Jan 6:169918. doi: 10.1016/j.scitotenv.2024.169918.
Yifan Zhang 1 Liugen Zheng 2 Dong Cheng 3 Changting Lei 1 Hui Li 3 Jun Zhou 1 Cuili Zhang 1 Fuyong Song 1 Tao Zeng 4 Xiulan Zhao 5
Affiliations

Affiliations

  • 1 Institute of Toxicology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
  • 2 Hainan Province Center for Disease Control and Prevention, Haikou 570203, China.
  • 3 Shandong Center for Disease Control and Prevention, Jinan 250014, China.
  • 4 Institute of Toxicology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China. Electronic address: zengtao@sdu.edu.cn.
  • 5 Institute of Toxicology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China. Electronic address: zhao.xl@sdu.edu.cn.
Abstract

Di(2-ethylhexyl) phthalate (DEHP) is a widely used plastic additive with persistent characteristics in the environment. This study was designed to investigate the detrimental effects of chronic DEHP exposure at environmental-relevant doses on bone metabolism and the underlying mechanisms. It was found that exposure to 25 μg/kg bw and 50 μg/kg bw DEHP for 29 weeks led to a reduction of whole-body bone mineral density (BMD), femur microstructure damage, decreased femur new bone formation, and increased femur bone marrow adipogenesis in C57BL/6 female mice, which was not observed in mice exposed to 5000 μg/kg bw DEHP. Further in vitro study showed that DEHP treatment robustly promoted adipogenic differentiation and suppressed osteogenic differentiation of the bone marrow mesenchymal stem cells (BMSCs). Mechanistically, DEHP exposure resulted in elevated expressions of DYRK1B, CDK5, PPARγ, and p-PPARγSer273 in both femur tissue and BMSCs. Interestingly, co-IP analysis showed potential interactions among DYRK1B, PPARγ, and CDK5. Lastly, antagonists of DYRK1B and CDK5 effectively alleviated the BMSCs differentiation disturbance induced by DEHP. These results suggest that DEHP may disturb the BMSCs differentiation by upregulating the PPARγ signaling which may be associated with the activation of DYRK1B and CDK5.

Keywords

Adipogenesis; Bone remodeling; Di(2-ethylhexyl) phthalate; Dual-specificity tyrosine phosphorylation-regulated kinase 1 B; Osteogenesis.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12277
    99.98%, DYRK1B抑制剂