邻苯二甲酸盐
脂肪生成
骨矿物
化学
股骨
内分泌学
间充质干细胞
骨髓
内科学
骨质疏松症
细胞生物学
生物
医学
外科
有机化学
作者
Yifan Zhang,Liugen Zheng,Dong Cheng,Changting Lei,Hui Li,Jun Zhou,Cuili Zhang,Fuyong Song,Tao Zeng,Xiulan Zhao
标识
DOI:10.1016/j.scitotenv.2024.169918
摘要
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 bone 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.
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