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TBBPA 暴露在体外和体内模型中都会导致软骨细胞损伤。

TBBPA exposure causes cartilage cell damage in both in vitro and in vivo models.

机构信息

Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; National Center for Orthopedics, Shanghai Sixth People's Hospital, Shanghai, China.

出版信息

Ecotoxicol Environ Saf. 2024 Nov 15;287:117271. doi: 10.1016/j.ecoenv.2024.117271. Epub 2024 Nov 12.

DOI:10.1016/j.ecoenv.2024.117271
PMID:39531942
Abstract

Tetrabromobisphenol A (TBBPA) is a widely used flame retardant. TBBPA is a persistent pollutant that is difficult to degrade and causes sustained pollution to the environment. TBBPA has been detected in human blood and tissues, and studies indicate it causes various toxicological damages to tissues and cells. To date, the toxicological effects of TBBPA on chondrocytes are not fully understood. Here, we evaluated the toxicological effects of TBBPA on chondrocytes and tissues. For this, human- and mouse-derived chondrocyte models were used to analyze the toxicological effects of TBBPA. Physiological concentrations of TBBPA were used to stimulate chondrocytes. Indirect immunofluorescence, flow cytometry, and biochemical assays were utilized to investigate TBBPA's toxicological impact on chondrocytes. The CCK8 experiment indicated that TBBPA reduced chondrocyte proliferation. ELISA and Western blot results indicated that TBBPA increased inflammatory factor expression in chondrocytes. We also found that TBBPA caused oxidative stress in chondrocytes. Mechanistic study showed that TBBPA triggered a imbalance in the homeostasis of calcium ions, leading to mitochondrial depolarization, which induces inflammation and oxidative stress of chondrocytes. In vivo model, our research showed that TBBPA caused inflammation in knee joint cartilage. Safranin O-Fast Green and H&E staining revealed cartilage tissue damage following TBBPA treatment. TBBPA increased MMP9 and MMP13 expression and down-regulated COL2 expression. In summary, we assessed TBBPA's impact on chondrocytes. The experimental data indicate that TBBPA causes damage to chondrocytes. This study establishes a basis for future research on the toxicological impacts of TBBPA.

摘要

四溴双酚 A(TBBPA)是一种广泛使用的阻燃剂。TBBPA 是一种难降解的持久性污染物,会对环境造成持续的污染。TBBPA 已在人体血液和组织中被检测到,研究表明它会对组织和细胞造成各种毒性损伤。迄今为止,TBBPA 对软骨细胞的毒性作用尚未完全了解。在这里,我们评估了 TBBPA 对软骨细胞和组织的毒性作用。为此,使用人源和鼠源软骨细胞模型来分析 TBBPA 的毒性作用。使用生理浓度的 TBBPA 刺激软骨细胞。间接免疫荧光、流式细胞术和生化分析用于研究 TBBPA 对软骨细胞的毒性影响。CCK8 实验表明 TBBPA 降低了软骨细胞的增殖。ELISA 和 Western blot 结果表明 TBBPA 增加了软骨细胞中炎症因子的表达。我们还发现 TBBPA 导致软骨细胞发生氧化应激。机制研究表明,TBBPA 引发钙离子平衡失调,导致线粒体去极化,从而引起软骨细胞的炎症和氧化应激。在体内模型中,我们的研究表明 TBBPA 导致膝关节软骨炎症。番红 O-快绿和 H&E 染色显示 TBBPA 处理后软骨组织损伤。TBBPA 增加了 MMP9 和 MMP13 的表达,降低了 COL2 的表达。综上所述,我们评估了 TBBPA 对软骨细胞的影响。实验数据表明 TBBPA 对软骨细胞造成损伤。本研究为未来研究 TBBPA 的毒性作用奠定了基础。

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