title: Synergistic effects of tributyltin and 2,3,7,8-tetrachlorodibenzo-p-dioxin on differentiating osteoblasts and osteoclasts.
abstract: The purpose of this study was to examine the effects of the persistent and accumulative environmental pollutants tributyltin (TBT) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) individually and in combination on differentiating bone cells. TBT and TCDD are chemically distinct compounds with different mechanisms of toxicity, but they typically have the same sources of exposure and both have been shown to affect bone development at low exposure levels. Bone marrow stem cells were isolated from femurs and tibias of C57BL/6J mice, differentiated in culture into osteoblasts or osteoclasts and exposed to 0.1-10nM TBT, 0.01-1nM TCDD or 10nM TBT+ 1nM TCDD. In osteoblasts, the combined exposure to TBT and TCDD significantly decreased the mRNA expression of alkaline phosphatase and osteocalcin more than TBT or TCDD alone. PCR array showed different gene expression profiles for TBT and TCDD individually, and the combination evoked several additional alterations in gene expression. Expression of aryl hydrocarbon receptor repressor (AHRR) was increased by TCDD as expected, but simultaneous exposure to TBT prevented the increase thus potentially strengthening AHR-mediated effects of TCDD. The number of osteoclasts was reduced by TCDD alone and in combination with TBT, but TBT alone had no effect. However, the total area of resorbed bone was remarkably lower after combined exposure than after TBT or TCDD alone. In conclusion, very low concentrations of TBT and TCDD have synergistic deleterious effects on bone formation and additive effects on bone resorption.
authors: University of Oulu, Department of Anatomy and Cell Biology, Oulu, Finland. antti.koskela@oulu.fi
authors: Antti
authors: A
authors: Koskela
authors: Matti
authors: M
authors: Viluksela
authors: Meeri
authors: M
authors: Keinänen
authors: Juha
authors: J
authors: Tuukkanen
authors: Merja
authors: M
authors: Korkalainen
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D001862:Bone Resorption / Q000139:chemically induced; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D005269:Femur / Q000166:cytology; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism; D013977:Tibia / Q000166:cytology; D014220:Trialkyltin Compounds / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D014220:Trialkyltin Compounds; C011559:tributyltin