{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:59:55Z","timestamp":1790164795458,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,9,23]],"date-time":"2014-09-23T00:00:00Z","timestamp":1411430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"name":"National Institute for Health Research Biomedical Research Fellowship","award":["BRF-2011-013"],"award-info":[{"award-number":["BRF-2011-013"]}]},{"name":"National Institute for Health Research Biomedical Research Fellowship","award":["BRF-2011-020"],"award-info":[{"award-number":["BRF-2011-020"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>Cobalt and chromium species are released in the local tissues as a result of tribo\u2010corrosion, 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\u2010ray fluorescence (XRF), X\u2010ray absorption spectroscopy (XAS), and fluorescent\u2010probing approaches of candidate receptors P2X7R and divalent metal transporter\u20101 (DMT\u20101), to better understand the entry, intra\u2010cellular 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 Cr<jats:sup>6+<\/jats:sup> to Cr<jats:sup>3+<\/jats:sup> was the only redox change observed in cells treated with Co<jats:sup>2+<\/jats:sup>, Cr<jats:sup>3+<\/jats:sup>, and Cr<jats:sup>6+<\/jats:sup>. Our data suggest that the cellular uptake and processing of Co and Cr differs between osteoblasts and osteoclasts. \u00a9 2014 The Authors. <jats:italic>Journal of Orthopaedic Research<\/jats:italic> published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 33:114\u2013121, 2015.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jor.22729","type":"journal-article","created":{"date-parts":[[2014,9,23]],"date-time":"2014-09-23T07:45:19Z","timestamp":1411458319000},"page":"114-121","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Understanding the tissue effects of tribo\u2010corrosion: Uptake, distribution, and speciation of cobalt and chromium in human bone cells"],"prefix":"10.1002","volume":"33","author":[{"given":"Karan M.","family":"Shah","sequence":"first","affiliation":[{"name":"Department of Human Metabolism The Mellanby Centre for Bone Research The University of Sheffield Beech Hill Road Sheffield S10 2RX United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Quinn","sequence":"additional","affiliation":[{"name":"Science Division Diamond Light Source Harwell Science and Innovations Campus Didcot Oxon OX11 0DE United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Gartland","sequence":"additional","affiliation":[{"name":"Department of Human Metabolism The Mellanby Centre for Bone Research The University of Sheffield Beech Hill Road Sheffield S10 2RX United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Mark","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"Department of Human Metabolism The Mellanby Centre for Bone Research The University of Sheffield Beech Hill Road Sheffield S10 2RX United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,9,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.22652"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.93B6.25804"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.H.00672"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2012-001541"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.06.007"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/000164702320155400"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.21581"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066186"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1039\/a707100k"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1103524"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2009.02.024"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2001.16.5.846"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-002-2098-y"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/41343"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.91B10.22308"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.J.01884"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0909049509032282"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sab.2006.12.002"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0909049505012719"},{"key":"e_1_2_6_21_1","unstructured":"2007 American Institute of Physics Melville NY A Tenderholt KO. Hodgson BP Hedman PySpline: a modern cross\u2010platform program for the processing of raw averaged XAS edge and EXAFS data 105 107"},{"key":"e_1_2_6_22_1","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1093\/jn\/132.4.693","article-title":"Iron treatment downregulates DMT1 and IREG1 mRNA expression in Caco\u20102 cells","volume":"132","author":"Martini LA","year":"2002","journal-title":"J Nutr"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2006.09.003"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0921-8777(96)00052-3"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0909049513001647"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.20831"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5310.266"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2cc33016d"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2012.05.003"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.3109\/10408444.2013.779633"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI102403"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.32700"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1247\/csf.12.251"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2008.12.028"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx9003402"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:MCBI.0000007274.25052.82"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4889(87)90044-9"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph6020643"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2010.06.006"}],"container-title":["Journal of Orthopaedic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjor.22729","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjor.22729","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.22729","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jor.22729","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.22729","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T19:25:39Z","timestamp":1696361139000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jor.22729"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,23]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1]]}},"alternative-id":["10.1002\/jor.22729"],"URL":"https:\/\/doi.org\/10.1002\/jor.22729","archive":["Portico"],"relation":{},"ISSN":["0736-0266","1554-527X"],"issn-type":[{"value":"0736-0266","type":"print"},{"value":"1554-527X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,23]]},"assertion":[{"value":"2014-03-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-08-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-09-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}