Department of Preventive Medicine, Shantou University Medical College, Shantou, 515041, Guangdong, China.
Department of Health Statistics, School of Public Health, Shanxi Medical University, 030001, Taiyuan, China.
Environ Pollut. 2024 Apr 15;347:123731. doi: 10.1016/j.envpol.2024.123731. Epub 2024 Mar 6.
Bisphenol A (BPA), an ingredient in consumer products, has been suggested that it can interfere with bone development and maintenance, whereas the molecule mechanism remains unclear. The objective of this study is to investigate the effect of BPA on early bone differentiation and metabolism, and its potential molecule mechanism by employing hFOB1.19 cell as an in vitro model, as well as larval zebrafish as an in vivo model. The in vitro experiments indicated that BPA decreased cell viability, inhibited osteogenic activity (such as ALP, RUNX2), increased ROS production, upregulated transcriptional or protein levels of apoptosis-related molecules (such as Caspase 3, Caspase 9), while suppressed transcriptional or protein levels of pyroptosis-specific markers (TNF-α, TNF-β, IL-1β, ASC, Caspase 1, and GSDMD). Moreover, the evidences from in vivo model demonstrated that exposure to BPA distinctly disrupted pharyngeal cartilage, craniofacial bone development, and retarded bone mineralization. The transcriptional level of bone development-related genes (bmp2, dlx2a, runx2, and sp7), apoptosis-related genes (bcl2), and pyroptosis-related genes (cas1, nlrp3) were significantly altered after treating with BPA in zebrafish larvae. In summary, our study, combining in vitro and in vivo models, confirmed that BPA has detrimental effects on osteoblast activity and bone development. These effects may be due to the promotion of apoptosis, the initiation of oxidative stress, and the inhibition of pyroptosis.
双酚 A（BPA）是一种存在于消费品中的成分，有研究表明它可能干扰骨骼的发育和维持，但其分子机制尚不清楚。本研究旨在通过体外 hFOB1.19 细胞模型和体内幼鱼斑马鱼模型，研究 BPA 对早期骨分化和代谢的影响及其潜在的分子机制。体外实验表明，BPA 降低细胞活力，抑制成骨活性（如碱性磷酸酶、RUNX2），增加 ROS 产生，上调凋亡相关分子（如 Caspase 3、Caspase 9）的转录或蛋白水平，同时抑制焦亡特异性标志物（TNF-α、TNF-β、IL-1β、ASC、Caspase 1 和 GSDMD）的转录或蛋白水平。此外，体内模型的研究结果表明，BPA 暴露明显破坏咽软骨、颅面骨发育和骨矿化。在幼鱼中用 BPA 处理后，骨发育相关基因（bmp2、dlx2a、runx2 和 sp7）、凋亡相关基因（bcl2）和焦亡相关基因（cas1、nlrp3）的转录水平显著改变。总之，本研究通过体外和体内模型证实，BPA 对成骨细胞活性和骨发育有不良影响。这些影响可能是由于促进细胞凋亡、引发氧化应激和抑制焦亡所致。
