title: Understanding the tissue effects of tribo-corrosion: uptake, distribution, and speciation of cobalt and chromium in human bone cells.
abstract: Cobalt and chromium species are released in the local tissues as a result of tribo-corrosion, and affect bone cell survival and function. However we have little understanding of the mechanisms of cellular entry, intracellular distribution, and speciation of the metals that result in impaired bone health. Here we used synchrotron based X-ray fluorescence (XRF), X-ray absorption spectroscopy (XAS), and fluorescent-probing approaches of candidate receptors P2X7R and divalent metal transporter-1 (DMT-1), to better understand the entry, intra-cellular distribution and speciation of cobalt (Co) and chromium (Cr) in human osteoblasts and primary human osteoclasts. We found that both Co and Cr were most highly localized at nuclear and perinuclear sites in osteoblasts, suggesting uptake through cell membrane transporters, and supported by a finding that P2X7 receptor blockade reduced cellular entry of Co. In contrast, metal species were present at discrete sites corresponding to the basolateral membrane in osteoclasts, suggesting cell entry by endocytosis and trafficking through a functional secretory domain. An intracellular reduction of Cr6+ to Cr3+ was the only redox change observed in cells treated with Co2+, Cr3+, and Cr6+. Our data suggest that the cellular uptake and processing of Co and Cr differs between osteoblasts and osteoclasts.
authors.affiliation: Department of Human Metabolism, The Mellanby Centre for Bone Research, The University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, United Kingdom.
authors.forename: Karan M
authors.initials: KM
authors.lastname: Shah
authors.forename: Paul D
authors.initials: PD
authors.lastname: Quinn
authors.forename: Alison
authors.initials: A
authors.lastname: Gartland
authors.forename: J Mark
authors.initials: JM
authors.lastname: Wilkinson
mesh_terms: D001842:Bone and Bones / Q000166:cytology / Q000000981:diagnostic imaging / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002857:Chromium / Q000378:metabolism*; D003035:Cobalt / Q000378:metabolism*; D003343:Corrosion; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000000981:diagnostic imaging / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000000981:diagnostic imaging / Q000378:metabolism*; D010014:Osteolysis; D010084:Oxidation-Reduction; D011859:Radiography; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism; D013052:Spectrometry, X-Ray Emission; D056928:X-Ray Absorption Spectroscopy; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D027682:Cation Transport Proteins; D002857:Chromium; D003035:Cobalt; D058486:Receptors, Purinergic P2X7; D000099236:Solute Carrier Family 11, Member 2
keywords: cobalt alloy; metal toxicity; osteoblast; osteoclast; osteolysis