Hypoxia‐like effect of Cobalt Chromium alloy micro particles on fibroblasts in vitro

Abstract

Periprosthetic osteolysis leading to asceptic loosening remains the primary cause of failure of joint replacement. Although many inflammatory cell types have been implicated, the exact pathomechanisms of asceptic loosening have not been delineated. 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-5 were cultured with Cobalt Chromium (CoCr ASTM F-75, 1-7 mm) particles. Cells were harvested after 72 h incubation and total cellular proteins extracted for downstream analysis via 2D Gel Electrophoresis and tandem mass spectrometry using MALDI-TOF-TOF-MS. Thirteen protein spots showed greater than twofold increase, following 72 h 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-myc downstream regulated gene 1 protein. Cobalt is a hypoxia mimicking agent and N-myc 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. ß

Does chronic raise of metal ion levels induce oxidative DNA damage and hypoxia‐like response in patients with metal‐on‐metal hip resurfacing?

“…the periprosthetic tissue reaction, further alter this condition . In such condition, cobalt, and chromium have been demonstrated to elicit a hypoxia‐like response that, if unchecked, can lead to unusual peri‐implant pathologies …”

Mesotubular‐Structured Hybrid Membrane Nanocontainer for Periodical Monitoring, Separation, and Recovery of Cobalt Ions from Water

“…Cobalt is a natural mineral nutrient for living organisms (i.e., animals). A minute amount of cobalt is a crucial component in the fabrication of cobalamin (i.e., vitamin B12) . Exposure to excessive levels of cobalt is toxic to the human body .…”

“…Am inute amount of cobalti sac rucial component in the fabrication of cobalamin (i.e.,v itamin B12). [30] Exposure to excessive levels of cobalt is toxic to the human body. [31] Cobalt is used in ad iverse range of manufacturing applications, including rechargeable batteries, radiotherapy,p ermanent magnets, aircraft engines, dentala nd medicalp rostheses,p igments,a nd tires.…”

Lipid‐transfer proteins

“…The particles were spherical in shape with smooth surface morphology. They were of 1–7 μm size with majority of the particles being in the 3–4 μm size range and were tested negative for endotoxin (Madathil et al, 2010).…”