title: Autoinflammation Around AES Total Ankle Replacement Implants.
abstract: BACKGROUND
  Failure of total ankle replacement (TAR) can be characterized by early peri-implant osteolysis even in the presence of very modest numbers of wear particles. The hypothesis of the study was that this reaction is in part mediated by autoinflammatory responses mediated via damage-associated molecular patterns (DAMPs, danger signals) and pattern-recognizing danger signal receptors (PRRs).
  
  
  METHODS
  Peri-implant tissue and control samples from 10 patients with AES implants were immunostained for hypoxia inducible factor-1α (HIF-1α), activated caspase-3, high-mobility group box 1 (HMGB1), receptor for advanced glycation end product (RAGE), and toll-like receptors TLR2 and TLR4. Results were evaluated on a 0 to 4 scale (from 0% to >50% stained area).
  
  
  RESULTS
  Peri-implant tissue around failed TAR implants had a relatively high mean HIF-1α score of 3 on a scale, which however was similar in control samples. HMGB1 (a DAMP) was seen to be mobilized from nuclei to cellular cytoplasm, and the active caspase-3(+) cells were increased. All PRRs were increased in revision samples.
  
  
  CONCLUSIONS
  Increased expression of HMGB1 and other danger signals together with increased PRR-dependent responsiveness could contribute to autoinflammatory peri-implantitis, multilocular cyst formation, and osteolysis in failed TAR implants.
  
  
  METHODS
  Level IV, case series.
authors.affiliation: Hospital Terveystalo Pulssi, and University of Turku, Turku, Finland helka.koivu@gmail.com.
authors.forename: Helka
authors.initials: H
authors.lastname: Koivu
authors.affiliation: Institute of Clinical Medicine, Department of Medicine, UH/HUCH, Helsinki, Finland Department of Orthopedics, Yamagata School of Medicine, Yamagata, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Takakubo
authors.affiliation: Institute of Clinical Medicine, Department of Medicine, UH/HUCH, Helsinki, Finland State Research Institute Center for Innovative Medicine, Vilnius, Lithuania.
authors.forename: Zygmunt
authors.initials: Z
authors.lastname: Mackiewicz
authors.affiliation: Institute of Clinical Medicine, Department of Medicine, UH/HUCH, Helsinki, Finland.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Al-Samadi
authors.affiliation: Institute of Clinical Medicine, Department of Medicine, UH/HUCH, Helsinki, Finland ORTON Orthopaedic Hospital of the ORTON Foundation, Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Soininen
authors.affiliation: Institute of Clinical Medicine, Department of Medicine, UH/HUCH, Helsinki, Finland.
authors.forename: Nitai
authors.initials: N
authors.lastname: Peled
authors.affiliation: State Research Institute Center for Innovative Medicine, Vilnius, Lithuania.
authors.forename: Modestas
authors.initials: M
authors.lastname: Kukis
authors.affiliation: Institute of Clinical Medicine, Department of Medicine, UH/HUCH, Helsinki, Finland.
authors.forename: Nina
authors.initials: N
authors.lastname: Trokovic
authors.affiliation: Institute of Clinical Medicine, Department of Medicine, UH/HUCH, Helsinki, Finland ORTON Orthopaedic Hospital of the ORTON Foundation, Helsinki, Finland.
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
mesh_terms: D058737:Arthroplasty, Replacement, Ankle; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D007595:Joint Prosthesis; D010014:Osteolysis / Q000378:metabolism* / Q000473:pathology; D011475:Prosthesis Failure; D051192:Receptors, Pattern Recognition / Q000378:metabolism; D012086:Reoperation; D013583:Synovial Membrane / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D015415:Biomarkers; C497442:HIF1A protein, human; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051192:Receptors, Pattern Recognition; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D053148:Caspase 3
keywords: HIF-1α; HMGB1; RAGE; TLR; ankle replacement implants; caspase-3; osteolysis