title: In vivo response of heme-oxygenase-1 to metal ions released from metal-on-metal hip prostheses.
abstract: 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.
authors.affiliation: Medical Technology Laboratory, Rizzoli RIT Department ‑ Research, Innovation and Technology, Rizzoli Orthopaedic Institute, I‑40136 Bologna, Italy.
authors.forename: Alina
authors.initials: A
authors.lastname: Beraudi
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, (DIMES), Unit of Histology, Embryology and Applied Biology, University of Bologna, I‑40136 Bologna, Italy.
authors.forename: Eva
authors.initials: E
authors.lastname: Bianconi
authors.affiliation: Unit of Occupational Health and Industrial Hygiene, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, I‑25100 Brescia, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Catalani
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, (DIMES), Unit of Histology, Embryology and Applied Biology, University of Bologna, I‑40136 Bologna, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Canaider
authors.affiliation: Medical Technology Laboratory, Rizzoli RIT Department ‑ Research, Innovation and Technology, Rizzoli Orthopaedic Institute, I‑40136 Bologna, Italy.
authors.forename: Dalila
authors.initials: D
authors.lastname: De Pasquale
authors.affiliation: Unit of Occupational Health and Industrial Hygiene, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, I‑25100 Brescia, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Apostoli
authors.affiliation: Medical Technology Laboratory, Rizzoli RIT Department ‑ Research, Innovation and Technology, Rizzoli Orthopaedic Institute, I‑40136 Bologna, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bordini
authors.affiliation: Medical Technology Laboratory, Rizzoli RIT Department ‑ Research, Innovation and Technology, Rizzoli Orthopaedic Institute, I‑40136 Bologna, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Stea
authors.affiliation: Medical Technology Laboratory, Rizzoli RIT Department ‑ Research, Innovation and Technology, Rizzoli Orthopaedic Institute, I‑40136 Bologna, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Toni
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, (DIMES), Unit of Histology, Embryology and Applied Biology, University of Bologna, I‑40136 Bologna, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Facchin
mesh_terms: D000368:Aged; D005260:Female; D015870:Gene Expression; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism*; D006622:Hip Prosthesis; D006801:Humans; D007477:Ions / Q000097:blood / Q000652:urine; D008297:Male; D061825:Metal-on-Metal Joint Prostheses / Q000009:adverse effects; D008670:Metals / Q000097:blood / Q000652:urine; D008875:Middle Aged
chemical_list: D007477:Ions; D008670:Metals; D051547:Heme Oxygenase-1