In vivo response of heme-oxygenase-1 to metal ions released from metal-on-metal hip prostheses

Metal ion release and accumulation is considered to be a factor responsible for the high failure rates of metal-on-metal (MoM) hip implants. Numerous studies have associated the presence of these ions, besides other factors, including a hypoxia-like response and changes in pH due to metal corrosion leading to the induction of the oxidative stress response. The aim of the present study was to verify whether, in patients with a MoM hip prosthesis, mRNA and protein expression of HMOX-1 was modulated by the presence of metal ions and whether patients without prostheses exhibit a different expression pattern of this enzyme. The study was conducted on 22 matched pairs of patients with and without prostheses, for a total of 44 samples. Ion dosage was determined using inductively coupled plasma mass spectrometry equipped with dynamic cell reaction. HMOX-1 gene expression was quantified by reverse transcription-quantitative polymerase chain reaction and HMOX-1 protein expression was analyzed using an enzyme-linked immunosorbent assay. The results demonstrated that although there were significant differences in the metallic ion concentrations amongst the two groups of patients, there was no correlation between circulating levels of cobalt (Co) and chromium (Cr), and HMOX-1 gene and protein expression. Additionally, there was no significant difference in the protein expression levels of HMOX-1 between the two groups. In conclusion, it was demonstrated that circulating Co and Cr ions released by articular prosthetics do not induce an increase in HMOX-1 mRNA and protein expression at least 3.5 years after the implant insertion. The present study suggests that involvement of HMOX-1 may be excluded from future studies and suggests that other antioxidant enzymes, including superoxide dismutase, glutathione peroxidase and reductase should be investigated.