title: Dense innervation in pseudocapsular tissue compared to aneural interface tissue in loose totally replaced hips.
abstract: BACKGROUND
  The function of many inflammatory cells is in part regulated by neuronal cells, which may lead to so-called neurogenic inflammation. Sensory nerves also mediate the pain sensation.
  
  
  METHODS
  This immunohistochemical study focused on visualization of C-sensory and sympathetic innervation in the synovial membrane-like interface and pseudocapsular tissue around loosened total hip replacement.
  
  
  RESULTS
  The synovial membrane-like interface did not contain C-sensory peptidergic or sympathetic neural structures. Only limited attempts to neural regeneration were detected. In contrast, pseudocapsule expressed dense innervation with strong CPON-ir sympathetic innervation and osteoarthritis also had C-sensory fibers. Intense neural regeneration was seen in these synovial membranes. Surprisingly, stellate and/or highly dendritic fibroblast-like cells in the fibrotic areas in the interface tissue expressed strong immunoreactivity to the neural marker PGP 9.5, ubiquitin carboxyterminal hydrolase.
  
  
  CONCLUSIONS
  Pain related to aseptic loosening cannot arise in the aneural interface membrane. Inflammation in interface/aseptic loosening seems to be driven by non-neurogenic factors, such as foreign bodies and micromovement. Insufficient lysosomal degradation of denatured proteins causes accumulation of ubiquitinated conjugates and enzymes involved in the process. This leads to insufficient degradation of platelet derived growth factor (PDGF)-receptor complex and can contribute to the accumulation of connective tissue in the interface. Failure in ubiquitin mediated proteolysis might support overgrowth of interface tissue and aseptic loosening.
authors.affiliation: Department of Oral Pathology and Oral Medicine, Institute of Dentistry, University of Helsinki, Finland.
authors.forename: Sirkku
authors.initials: S
authors.lastname: Niissalo
authors.forename: Tiang-Fang
authors.initials: TF
authors.lastname: Li
authors.forename: Seppo
authors.initials: S
authors.lastname: Santavirta
authors.forename: Michiaki
authors.initials: M
authors.lastname: Takagi
authors.forename: Jarkko
authors.initials: J
authors.lastname: Hietanen
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
mesh_terms: D000320:Adrenergic Fibers / Q000201:enzymology / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019644:Arthroplasty, Replacement, Hip; D005260:Female; D005549:Foreign-Body Reaction / Q000209:etiology / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007593:Joint Instability / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009416:Nerve Regeneration; D009419:Nerve Tissue Proteins / Q000032:analysis; D015207:Osteoarthritis, Hip / Q000601:surgery; D011475:Prosthesis Failure; D012086:Reoperation; D011984:Sensory Receptor Cells / Q000201:enzymology / Q000473:pathology; D013583:Synovial Membrane / Q000294:innervation* / Q000473:pathology; D013869:Thiolester Hydrolases / Q000032:analysis; D043222:Ubiquitin Thiolesterase
chemical_list: D009419:Nerve Tissue Proteins; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase