Wejheden Carolina, Brunnberg Sara, Hanberg Annika, Lind P Monica
Division of Biochemical Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Biochem Biophys Res Commun. 2006 Mar 3;341(1):116-20. doi: 10.1016/j.bbrc.2005.12.158. Epub 2006 Jan 6.
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine disrupting environmental pollutant that, among other effects, affects bone tissue. TCDD modulates the transcription of various genes, e.g., CYP1A1, and the present study is a part of a project aiming at developing an in vitro model system for identifying biomarkers specific for dioxin-induced effects in osteoblasts. Osteopontin (OPN) is an adhesion protein, suggested to be important in bone remodeling and our results indicate that TCDD down-regulates the transcription of OPN in the osteoblastic cell line, UMR-106. The present study shows that UMR-106 expresses the AhR and that the expression of CYP1A1 is induced after exposure to TCDD, while down-regulation of OPN is an even more rapid response and a sensitive biomarker to TCDD exposure in this osteoblastic cell line. In conclusion, this osteoblastic cell line may be used as an in vitro model-system for studying dioxin-induced effects on osteoblasts.
2,3,7,8-四氯二苯并对二恶英(TCDD)是一种具有内分泌干扰作用的环境污染物,除其他影响外,还会影响骨组织。TCDD可调节多种基因(如CYP1A1)的转录,本研究是一个项目的一部分,该项目旨在开发一种体外模型系统,用于鉴定成骨细胞中对二恶英诱导效应具有特异性的生物标志物。骨桥蛋白(OPN)是一种黏附蛋白,被认为在骨重塑中起重要作用,我们的结果表明,TCDD可下调成骨细胞系UMR-106中OPN的转录。本研究表明,UMR-106表达芳烃受体(AhR),暴露于TCDD后CYP1A1的表达被诱导,而OPN的下调是一种更快的反应,并且是该成骨细胞系中TCDD暴露的敏感生物标志物。总之,这种成骨细胞系可作为研究二恶英对成骨细胞诱导效应的体外模型系统。