4-tert-octylphenol regulates the differentiation of C3H10T1/2 cells into osteoblast and adipocyte lineages
4-tert-octylphenol regulates the differentiation of C3H10T1/2 cells into osteoblast and adipocyte lineages
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DOI：
10.1093/toxsci/kfm296
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发表时间：
2008-03-01
影响因子：
3.8
通讯作者：
Masuno, Hiroshi
中科院分区：
文献类型：
--
作者：
Miyawaki, Joji;Kamei, Setsuya;Masuno, Hiroshi
本研究的目的是探讨4-叔辛基酚（OP）是否影响多能C3 H10 T1/2细胞，从小鼠胚胎结缔组织建立的细胞系，成骨细胞和脂肪细胞谱系的分化。将汇合的C3 H10 T1/2细胞与（OP处理的培养物）或不与（对照培养物）15 μ g/ml OP一起孵育7天。用OP处理汇合的细胞7天使碱性磷酸酶活性降低81%，抑制转化生长因子β 2的表达，并抑制细胞的形态学变化为成骨细胞外观。这些结果表明，用OP处理汇合的C3 H10 T1/2细胞7天抑制其向成骨细胞的分化。由于该处理强烈诱导过氧化物酶体增殖物激活受体r（PPARr）的表达，但不刺激细胞中三酰甘油（TG）的蓄积，因此将对照和OP处理培养物中的C3 H10 T1/2细胞与激素混合物（胰岛素[INS]、地塞米松和1-甲基-3-异丁基黄嘌呤）孵育2天，并与INS单独孵育另外5天。OP处理培养物的TG和脂联素含量分别是对照培养物的4.2和4.1倍。OP处理的培养物中油红O染色的细胞比对照培养物中的细胞多得多。OPARr在OP处理的培养物中的表达高于对照培养物。这些结果表明OP处理的培养物比对照培养物含有更多的脂肪细胞。总之，用OP处理C3 H10 T1/2细胞抑制成骨细胞分化，导致向脂肪细胞的谱系转变。
The aim of this study was to investigate whether 4-tert-octylphenol (OP) affects the differentiation of multipotent C3H10T1/2 cells, a cell line established from mouse embryonic connective tissue, into osteoblast and adipocyte lineages. Confluent C3H10T1/2 cells were incubated for 7 days with (OP-treated cultures) or without (control cultures) 15 mu g/ml of OP. The 7-day treatment of confluent cells with OP decreased alkaline phosphatase activity by 81%, inhibited the expression of transforming growth factor beta 2, and inhibited the morphological changes in cells to an osteoblastic appearance. These results indicate that the 7-day treatment of confluent C3H10T1/2 cells with OP inhibited their differentiation into osteoblasts. Since this treatment strongly induced the expression of peroxisome proliferator-activated receptor r (PPARr) but did not stimulate triacylglycerol (TG) accumulation in cells, C3H10T1/2 cells in the control and OP-treated cultures were incubated for 2 days with a hormone mixture (insulin [INS], dexamethasone, and 1-methyl-3-isobutylxanthine) and incubated for an additional 5 days with INS alone. The TG and adiponectin contents of the OP-treated cultures were 4.2 and 4.1 times higher, respectively, than those of the control cultures. There were many more Oil Red O-staining cells in the OP-treated cultures than in the control cultures. The expression of PPARr in the OP-treated cultures was higher than that in the control cultures. These results indicate that the OP-treated cultures contained a larger number of adipocytes than the control cultures. In conclusion, treatment of C3H10T1/2 cells with OP inhibited osteoblast differentiation, causing a lineage shift toward adipocytes.