%0 Journal Article
%T Complex toxicity as disruption of adipocyte or osteoblast differentiation in human mesenchymal stem cells under the mixed condition of TBBPA and TCDD
%A Ema Akiyama
%A Hideki Kakutani
%A Souichi Ohta
%A Teruyuki Nakao
%A Tomohiro Yuzuriha
%J Archive of "Toxicology Reports".
%D 2018
%R 10.1016/j.toxrep.2018.06.007
%X 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 PPAR¦Ã-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
%K ALP
%K alkaline phosphatase
%K aP2
%K adipocyte-specific protein 2
%K BFRs
%K brominated flame retardants
%K C/EBP¦Á
%K CCAAT-enhancer-binding protein alpha
%K DOHaD
%K developmental origins of health and disease
%K EDCs
%K endocrine-disrupting chemicals
%K LPL
%K lipoprotein lipase
%K MSC
%K mesenchymal stem cell
%K PCDDs/DFs
%K polychlorinated dibenzo-p-dioxins and dibenzofurans
%K PPAR¦Ã
%K peroxisome proliferator activated receptor gamma
%K RUNX2
%K runt-related transcription factor 2
%K TBBPA
%K tetrabromobisphenol A
%K TCDD
%K 2
%K 3
%K 7
%K 8-tetrachlorodibenzo-p-dioxin Tetrabromobisphenol A
%K 2
%K 3
%K 7
%K 8-tetrachlorodibenzo-p-dioxin
%K Human mesenchymal stem cell
%K Adipocyte differentiation
%K Osteoblast differentiation
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008500/