4-tert-octylphenol regulates the differentiation of C3H10T1/2 cells into osteoblast and adipocyte lineages.
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 microg/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 beta2, 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.
Department of Bone and Joint Surgery, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.
Joji
J
Miyawaki
Setsuya
S
Kamei
Kenshi
K
Sakayama
Haruyasu
H
Yamamoto
Hiroshi
H
Masuno
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001559:Benzhydryl Compounds; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D019070:Cell Lineage; D048430:Cell Shape / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004852:Epoxy Compounds / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D039902:Multipotent Stem Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D013997:Time Factors; D053781:Transforming Growth Factor beta2 / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D000098826:Bisphenol A Compounds
D052242:Adiponectin; D000469:Alkaline Phosphatase; D001559:Benzhydryl Compounds; D004852:Epoxy Compounds; D047492:Peroxisome Proliferator-Activated Receptors; D010636:Phenols; D053781:Transforming Growth Factor beta2; D014280:Triglycerides; D014874:Water Pollutants, Chemical; C499919:Adipoq protein, mouse; C019273:bisphenol A diglycidyl ether; D000098826:Bisphenol A Compounds; C041594:4-nonylphenol; C105260:4-tert-octylphenol