ToxSci Advance Access originally published online on December 7, 2007
Toxicological Sciences 2008 102(1):82-88; doi:10.1093/toxsci/kfm296
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4-Tert-Octylphenol Regulates the Differentiation of C3H10T1/2 Cells into Osteoblast and Adipocyte Lineages
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* Department of Bone and Joint Surgery, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan
Department of Medical Technology, Faculty of Health Sciences, Ehime Prefectural University of Health Sciences, Takooda, Tobe-cho, Iyo-gun, Ehime 791-2101, Japan
1 To whom correspondence should be addressed. Fax: +81-89-958-2177. E-mail: hmasuno{at}epu.ac.jp.
Received September 28, 2007; accepted December 5, 2007
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Abstract |
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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 µg/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 β2, 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.
Key Words: 4-tert-octylphenol; C3H10T1/2 cells; osteoblast differentiation; adipocyte differentiation.