title: Receptor activator of nuclear factor kappaB ligand is expressed in resident and inflammatory cells in aseptic and septic prosthesis loosening.
abstract: OBJECTIVE
  The pathogenesis of periprosthetic bone loss in aseptic and septic prosthesis loosening is unclear. There is considerable evidence that macrophages and osteoclasts play a key role in focal bone erosion and osteolysis around the prosthesis. RANKL (receptor activator of nuclear factor kappaB ligand) was shown to be a potent osteoclastogenic factor, and to be involved in bone destruction of myeloma and rheumatoid arthritis patients. Osteoprotegerin (OPG) is the natural RANKL inhibitor and may prevent periprosthetic bone loss.
  
  
  METHODS
  The presence and distribution of RANKL, its receptor RANK and OPG in the periprosthetic interface of septically (n = 5) and aseptically (n = 6) loosened prostheses was examined by immunohistochemistry and immunoblotting. Additionally, the immunophenotype of the inflammatory infiltrate was determined [CD3, CD68, Ki-67, tartrate-resistant acid posphatase (TRAP)].
  
  
  RESULTS
  Aseptic and septic cases revealed a different histopathologic pattern. However, in all cases RANKL and RANK could be demonstrated in macrophages and giant cells. In addition, RANKL detected by immunoblot analysis proved to have the same molecular weight as a recombinant RANKL used as a control (31 kD and approximately 48 kD). OPG was detected in aseptic loosening, where macrophages showed a strong staining, but multinucleated giant cells were only weakly stained. A weak OPG staining was also observed in septic loosening.
  
  
  CONCLUSIONS
  The pathogenesis of bone loss in septic loosening remains unclear, because the septic membrane bears few macrophages and giant cells, and half of them express OPG. In aseptic loosening, macrophages might not be stimulated by RANKL as a result of OPG expression. But multinucleated giant cells may be activated, as they hardly express OPG. They might be responsible for periprosthetic bone loss in aseptic loosening as a result of their RANKL and RANK expression.
authors.affiliation: ENDO-Klinik Hamburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Gehrke
authors.forename: C
authors.initials: C
authors.lastname: Sers
authors.forename: L
authors.initials: L
authors.lastname: Morawietz
authors.forename: G
authors.initials: G
authors.lastname: Fernahl
authors.forename: J
authors.initials: J
authors.lastname: Neidel
authors.forename: L
authors.initials: L
authors.lastname: Frommelt
authors.forename: V
authors.initials: V
authors.lastname: Krenn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019644:Arthroplasty, Replacement, Hip; D019645:Arthroplasty, Replacement, Knee; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D005260:Female; D015726:Giant Cells / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins / Q000378:metabolism; D006622:Hip Prosthesis; D006801:Humans; D007150:Immunohistochemistry; D007720:Knee Prosthesis; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D010014:Osteolysis / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D053244:Osteoprotegerin; D011475:Prosthesis Failure; D016459:Prosthesis-Related Infections / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human