title: Inhibitory effects on osteoblast differentiation in vitro by the polychlorinated biphenyl mixture Aroclor 1254 are mainly associated with the dioxin-like constituents.
abstract: The polychlorinated biphenyl (PCB) mixture Aroclor 1254 alters bone tissue properties. However, the mechanisms responsible for the observed effects have not yet been clarified. This study compared the effect of Aroclor 1254 on the expression of osteoblast differentiation markers in MC3T3-E1 cells with the corresponding effect of the dioxin reference compound 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and two PCB congeners belonging to the category of non-dioxin-like PCBs. The aim of the study was to quantify the relative influence of dioxin-like and non-dioxin-like PCB-components on osteoblast differentiation. Expression of marker genes for AhR activity and osteoblast differentiation were analyzed, and relative potency (REP) values were derived from Benchmark concentration-effect curves. Expression of alkaline phosphatase and osteocalcin were decreased by both Aroclor 1254 and TCDD exposure, while the PCB-congeners PCB19 and PCB52 slightly induced the expression. The relative potency of Aroclor 1254 for inhibitory effects on osteoblast differentiation marker genes was within the expected range as estimated from the chemical composition of Aroclor 1254. These results are consistent with previously observed bone modulations following in vivo exposure to Aroclor 1254 and TCDD, and demonstrate that the inhibitory effects of Aroclor 1254 on osteoblast differentiation by the dioxin-like constituents are over-riding the contribution of non-dioxin-like PCBs.
authors: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors: Maria
authors: M
authors: Herlin
authors: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Mattias
authors: M
authors: Öberg
authors: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Joakim
authors: J
authors: Ringblom
authors: Department of Oncology-Pathology, Cancer Centrum Karolinska, Karolinska Institutet, Stockholm, Sweden.
authors: Bertrand
authors: B
authors: Joseph
authors: Department of Environmental Health, National Institute for Health and Welfare, Kuopio, Finland.
authors: Merja
authors: M
authors: Korkalainen
authors: Department of Environmental Health, National Institute for Health and Welfare, Kuopio, Finland; Department of Environmental Science, University of Eastern Finland, Kuopio, Finland.
authors: Matti
authors: M
authors: Viluksela
authors: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Rachel A
authors: RA
authors: Heimeier
authors: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: Helen.Hakansson@ki.se.
authors: Helen
authors: H
authors: Håkansson
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D000072317:Polychlorinated Dibenzodioxins; C493716:Runx2 protein, mouse; D015675:Osteocalcin; D020111:Chlorodiphenyl (54% Chlorine); D000469:Alkaline Phosphatase
keywords: Aroclor 1254; Aryl hydrocarbon receptor; Mixture toxicity; Osteoblast; TCDD; Toxic equivalency factors