title: Effects of developmental exposure to perfluorooctanoic acid (PFOA) on long bone morphology and bone cell differentiation.
abstract: Perfluorooctanoic acid (PFOA) is a ubiquitous and persistent environmental chemical, which has been used extensively due to its stability and surface tension-lowering properties. Toxicological effects include induction of neonatal mortality and reproductive toxicity. In this study, pregnant C57BL/6 mice were exposed orally to 0.3mg PFOA/kg/day throughout pregnancy, and female offspring were studied at the age of 13 or 17months. Morphometrical and biomechanical properties of femurs and tibias were analyzed with micro-computed tomography and 3-point bending, and bone PFOA concentrations were determined by mass spectrometry. The effects of PFOA on bone cell differentiation were studied in osteoclasts from C57BL/6 mice and in the MC3T3 pre-osteoblast cell line. PFOA exposed mice showed increased femoral periosteal area as well as decreased mineral density of tibias. Biomechanical properties of these bones were not affected. Bone PFOA concentrations were clearly elevated even at the age of 17months. In osteoblasts, low concentrations of PFOA increased osteocalcin (OCN) expression and calcium secretion, but at PFOA concentrations of 100μM and above osteocalcin (OCN) expression and calcium secretion were decreased. The number of osteoclasts was increased at all PFOA concentrations tested and resorption activity dose-dependently increased from 0.1-1.0μM, but decreased at higher concentrations. The results show that PFOA accumulates in bone and is present in bones until the old age. PFOA has the potential to influence bone turnover over a long period of time. Therefore bone is a target tissue for PFOA, and altered bone geometry and mineral density seem to persist throughout the life of the animal.
authors.affiliation: Institute of Cancer Research and Translational Medicine, MRC Oulu and Department of Anatomy and Cell Biology, Faculty of Medicine, University of Oulu, Oulu, Finland. Electronic address: antti.koskela@oulu.fi.
authors.forename: A
authors.initials: A
authors.lastname: Koskela
authors.affiliation: Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland.
authors.forename: M A
authors.initials: MA
authors.lastname: Finnilä
authors.affiliation: National Institute for Health and Welfare, Department of Health Protection, Kuopio, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Korkalainen
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Spulber
authors.affiliation: National Institute for Health and Welfare, Department of Health Protection, Kuopio, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Koponen
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Håkansson
authors.affiliation: Institute of Cancer Research and Translational Medicine, MRC Oulu and Department of Anatomy and Cell Biology, Faculty of Medicine, University of Oulu, Oulu, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Tuukkanen
authors.affiliation: National Institute for Health and Welfare, Department of Health Protection, Kuopio, Finland; Department of Environmental and Biological Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Viluksela
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities / Q000000981:diagnostic imaging / Q000187:drug effects*; D002210:Caprylates / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005466:Fluorocarbons / Q000633:toxicity*; D007774:Lactation; D008431:Maternal-Fetal Exchange; D059630:Mesenchymal Stem Cells; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics; D010010:Osteoclasts / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D055114:X-Ray Microtomography
chemical_list: D002210:Caprylates; D005466:Fluorocarbons; D015675:Osteocalcin; C023036:perfluorooctanoic acid; D000469:Alkaline Phosphatase
keywords: Bone toxicity; Osteogenesis; PFOA; Resorption; Stem cells