Complex toxicity as disruption of adipocyte or osteoblast differentiation in human mesenchymal stem cells under the mixed condition of TBBPA and TCDD.
Complex toxicity as disruption of adipocyte or osteoblast differentiation in human mesenchymal stem cells under the mixed condition of TBBPA and TCDD.
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DOI：
10.1016/j.toxrep.2018.06.007
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发表时间：
2018
影响因子：
--
通讯作者：
Ohta S
中科院分区：
文献类型：
--
作者：
Kakutani H;Yuzuriha T;Akiyama E;Nakao T;Ohta S
人们经常在无意中接触到食物和大气中的许多化合物，如环境污染物和内分泌干扰物(EDCs)。特别是，在人类母乳和身体中发现了扰乱内分泌的TBBPA和二恶英。传统的研究通过给细胞或动物注射一种物质来评估毒性，但评估这些摄入化合物的混合物的毒性对于“真正的”毒理学评估是必不可少的。我们使用人骨髓间充质干细胞(HMSCs)在体外评估了毒性效应。TbPA通过PPARγ依赖机制增加脂肪细胞脂滴数量，上调脂肪细胞相关基因aP2和Lp1的表达。TCDD抑制脂滴和脂肪细胞相关的mRNA水平。TBBPA促进脂肪细胞分化，TCDD抑制脂肪细胞分化，呈剂量依赖关系。TBBPA不影响成骨细胞的分化，但TCDD抑制ALP染色和活性、钙沉积和成骨细胞相关的mRNA水平。在TBBPA和TCDD的混合物中，TBBPA以剂量依赖的方式抑制TCDD抑制脂肪细胞和成骨细胞的分化。有趣的是，我们观察到经TBBPA处理的细胞中的脂滴分化为成骨细胞。这些结果表明，TBBPA和TCDD扰乱了向脂肪细胞和成骨细胞的分化，有助于更全面地了解接触这些化学物质的毒理学意义。
People are frequently and unintentionally exposed to many chemical compounds, such as environmental pollutants and endocrine-disrupting chemicals (EDCs), in food and from the atmosphere. In particular, endocrine-disrupting TBBPA and dioxins are found in human breast milk and in the body. Conventional studies evaluate toxicity by administering a single substance to cells or animals, but evaluation of the toxicity of mixtures of these ingested compounds is essential for “true” toxicological assessment. We evaluated toxic effects in vitro using human mesenchymal stem cells (hMSCs). TBBPA increased the number of lipid droplets, and upregulated the expression of adipocyte-related mRNA, aP2 and LPL, through a PPARγ-dependent mechanism. TCDD suppressed lipid droplets and adipocyte-related mRNA levels. Adipocyte differentiation was stimulated by TBBPA and inhibited by TCDD in a dose-dependent manner. TBBPA did not influence osteoblast differentiation, but TCDD suppressed ALP staining and activity, calcium deposition, and osteoblast-related mRNA levels. In a mixture of TBBPA and TCDD, TBBPA inhibited TCDD suppression of adipocyte and osteoblast differentiation in a dose-dependent manner. Interestingly, we observed lipid droplets in TBBPA-treated cells differentiated into osteoblasts. These results suggest that TBBPA and TCDD disrupted differentiation into adipocytes and osteoblasts and contributes to a more complete toxicological understanding of exposure to these chemical substances.