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In the present study we have adopted a proteomic approach to elucidate the initial signals that are expressed to particulate material, using an in vitro cell culture system. Human lung fibroblasts MRC\u20105 were cultured with Cobalt Chromium (CoCr ASTM F\u201075, 1\u20137\u2009\u00b5m) particles. Cells were harvested after 72\u2009h incubation and total cellular proteins extracted for downstream analysis via 2D Gel Electrophoresis and tandem mass spectrometry using MALDI\u2010TOF\u2010TOF\u2010MS. Thirteen protein spots showed greater than twofold increase, following 72\u2009h incubation of fibroblast with CoCr particles. Four of these proteins were identified by tandem mass spectrometry. These were Annexin II, Pyruvate kinase, Triose phosphate isomerase, and N\u2010myc downstream regulated gene 1 protein. Cobalt is a hypoxia mimicking agent and N\u2010myc downstream regulated gene 1 protein, Triose phosphate isomerase, Pyruvate kinase, and Annexin II are important hypoxia regulated gene products that are found to be over expressed in cellular oxidative stress response. Our data indicates that exposure of fibroblast to CoCr alloy induces the transition of these cells into a hypoxia like state and oxidative stress even in normoxic culture conditions. The study reflects the possibility of the presence of a hypoxic environment in the periprosthetic tissue surrounding metallic implants. Published by Wiley Periodicals, Inc. J Orthop Res 28:1360\u20131367, 2010<\/jats:p>","DOI":"10.1002\/jor.21133","type":"journal-article","created":{"date-parts":[[2010,3,26]],"date-time":"2010-03-26T19:52:54Z","timestamp":1269633174000},"page":"1360-1367","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Hypoxia\u2010like effect of Cobalt Chromium alloy micro particles on fibroblasts in vitro"],"prefix":"10.1002","volume":"28","author":[{"given":"Bernadette 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