title: Increased expression of a novel osteoclast-stimulating factor, ADAM8, in interface tissue around loosened hip prostheses.
abstract: OBJECTIVE
  ADAM8 is a protein of a disintegrin and a metalloproteinase family that can induce osteoclast fusion and activity, perhaps via interactions involving integrin receptors and their cysteine-rich/disintegrin domains. Because loosening of hip replacement implants is characterized by foreign body giant cells and peri-implant osteoclasts, it was speculated that this molecule might be (over)expressed in the synovial membrane-like interface tissues.
  
  
  METHODS
  In situ hybridization; immunohistochemical staining with or without tartrate-resistant acid phosphatase (TRAP) staining; image analysis/morphometry; isolation, amplification, and cloning of ADAM8; nucleotide sequencing; quantitative reverse transcriptase-polymerase chain reaction (RT-PCR); and Western blot.
  
  
  RESULTS
  In situ hybridization disclosed ADAM8 mRNA in mono- and multinuclear cells in both interface and control synovial samples. Quantitative RT-PCR revealed high ADAM8 mRNA copy numbers in interface tissue (p < 0.01). Accordingly, extensive ADAM8 immunoreactivity was observed in the lining-like layers and sublining areas of interface tissue (p < 0.001). A 65 kDa ADAM8 band in Western blot of tissue extracts confirmed these findings. ADAM8/TRAP double staining showed close spatial relationships of ADAM8 positive precursor cells with other precursors and/or TRAP-positive multinuclear cells.
  
  
  CONCLUSIONS
  ADAM8 is (over)expressed in tissues around aseptically loosened total hip implants, which are characterized by chronic foreign body inflammation and peri-implant bone loss. This is compatible with a role for ADAM8 in the formation of foreign body giant cells and osteoclasts.
authors.affiliation: Department of Anatomy, University of Helsinki, Helsinki, Finland.
authors.forename: Jami
authors.initials: J
authors.lastname: Mandelin
authors.forename: Tian-Fang
authors.initials: TF
authors.lastname: Li
authors.forename: Mika V J
authors.initials: MV
authors.lastname: Hukkanen
authors.forename: Mikko
authors.initials: M
authors.lastname: Liljeström
authors.forename: Zhan-Kun
authors.initials: ZK
authors.lastname: Chen
authors.forename: Seppo
authors.initials: S
authors.lastname: Santavirta
authors.forename: Uula
authors.initials: U
authors.lastname: Kitti
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001707:Biopsy, Needle; D016022:Case-Control Studies; D015331:Cohort Studies; D019483:Disintegrins / Q000032:analysis*; D005260:Female; D006622:Hip Prosthesis / Q000009:adverse effects*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D007593:Joint Instability / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000473:pathology / Q000601:surgery; D010455:Peptides / Q000032:analysis*; D011379:Prognosis; D011475:Prosthesis Failure; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D019483:Disintegrins; D047908:Intracellular Signaling Peptides and Proteins; D010455:Peptides; C408994:osteoclast stimulating factor