title: Perfluorooctanoic acid induces mitochondrial dysfunction in MC3T3-E1 osteoblast cells.
abstract: Perfluorooctanoic acid (PFOA), a stable organic perfluorinated compound, is an emerging persistent organic pollutant, found widely in human and wildlife populations. Recent evidence suggests that exposure to environmental toxicants can be associated with higher risks of osteoporosis and fractures. We studied the cellular toxicology of PFOA in MC3T3-E1osteoblast cells. To examine the effect of PFOA, we measured cell viability, reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial parameters including adenosine triphosphate (ATP) level, mitochondrial membrane potential (MMP), cardiolipin content, and cytochrome c release in MC3T3-E1 cells. Incubating MC3T3-E1 cells in different concentrations of PFOA for 48 h resulted in a concentration-dependent decrease in cell viability and significant inductions of ROS and mitochondrial superoxide. Moreover, PFOA induced MMP collapse, cardiolipin peroxidation, cytochrome c release, and decreased ATP levels, which in turn induced apoptosis or necrosis. When osteoblast differentiation markers were assessed, PFOA treatment caused a significant reduction in alkaline phosphatase activity, collagen synthesis, and mineralization in the cells. In summary, we found an ROS- and mitochondria-mediated pathway for the induction of cell damage by PFOA in MC3T3-E1 cells. Together, our results indicate that mitochondrial toxicity could be a plausible mechanism for the toxic effects of PFOA on osteoblast function.
authors.affiliation: a Department of Endocrinology and Metabolism , School of Medicine, Kyung Hee University , Seoul , Republic of Korea.
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Choi
authors.affiliation: b Research Institute of Endocrinology, Kyung Hee University Hospital , Seoul , Republic of Korea.
authors.forename: Kwang Sik
authors.initials: KS
authors.lastname: Suh
authors.affiliation: a Department of Endocrinology and Metabolism , School of Medicine, Kyung Hee University , Seoul , Republic of Korea.
authors.forename: Sang Youl
authors.initials: SY
authors.lastname: Rhee
authors.affiliation: a Department of Endocrinology and Metabolism , School of Medicine, Kyung Hee University , Seoul , Republic of Korea.
authors.forename: Seungjoon
authors.initials: S
authors.lastname: Oh
authors.affiliation: a Department of Endocrinology and Metabolism , School of Medicine, Kyung Hee University , Seoul , Republic of Korea.
authors.forename: Jeong-Taek
authors.initials: JT
authors.lastname: Woo
authors.affiliation: a Department of Endocrinology and Metabolism , School of Medicine, Kyung Hee University , Seoul , Republic of Korea.
authors.forename: Sung Woon
authors.initials: SW
authors.lastname: Kim
authors.affiliation: a Department of Endocrinology and Metabolism , School of Medicine, Kyung Hee University , Seoul , Republic of Korea.|c Department of Internal Medicine , Chung Hospital , Seongnam-si , Gyeonggi-do , Republic of Korea.
authors.forename: Young Seol
authors.initials: YS
authors.lastname: Kim
authors.affiliation: d Department of Physiology , Kyung Hee University, College of Medicine , Seoul , Republic of Korea.
authors.forename: Youngmi Kim
authors.initials: YK
authors.lastname: Pak
authors.affiliation: a Department of Endocrinology and Metabolism , School of Medicine, Kyung Hee University , Seoul , Republic of Korea.
authors.forename: Suk
authors.initials: S
authors.lastname: Chon
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002210:Caprylates / Q000633:toxicity*; D002460:Cell Line / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005466:Fluorocarbons / Q000633:toxicity*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D002210:Caprylates; D005466:Fluorocarbons; D017382:Reactive Oxygen Species; D014874:Water Pollutants, Chemical; C023036:perfluorooctanoic acid
keywords: Environmental toxicants; mitochondrial function; osteoblast; reactive oxygen species