title: Interface tissue fibroblasts from loose total hip replacement prosthesis produce receptor activator of nuclear factor-kappaB ligand, osteoprotegerin, and cathepsin K.
abstract: OBJECTIVE
  The highly osteolytic interface tissue between the bone and loosening total hip prosthesis is characterized by low pH, formation of foreign body giant cells, osteoclasts, and production of receptor activator of nuclear factor-kappaB (RANKL) and cathepsin K. We hypothesized that fibroblasts in the interface tissue may form a source for RANKL production.
  
  
  METHODS
  Primary interface tissue fibroblasts, fibrous joint capsule fibroblasts, and trabecular bone osteoblasts were stimulated with tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), IL-6, IL-11, or 1alpha,25-(OH)2 vitamin D3. Cellular RANKL and released cathepsin K were detected by Western blotting. RANKL in cell lysates and osteoprotegerin (OPG) in cell culture medium were measured by ELISA. RANKL, OPG, and cathepsin K mRNA were measured with quantitative reverse transcriptase polymerase chain reaction.
  
  
  RESULTS
  Interface tissue fibroblasts were found to produce RANKL. 1alpha,25-(OH)2 vitamin D3 stimulation increased RANKL mRNA expression. TNF-alpha was found to be the most potent OPG inducer in interface tissue fibroblasts. Cathepsin K mRNA production in fibroblasts was upregulated roughly 3-fold (p < 0.01) after 1alpha,25-(OH)2D3 stimulation, and both pro- and active cathepsin K protein was released to fibroblast culture media.
  
  
  CONCLUSIONS
  Interface tissue fibroblasts are able to produce RANKL, OPG, and cathepsin K and may contribute indirectly and directly to pathologic periprosthetic collagenolysis and bone destruction.
authors.affiliation: Institute of Biomedicine/Anatomy, Biomedicum Helsinki, 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
authors.initials: M
authors.lastname: Hukkanen
authors.forename: Mikko
authors.initials: M
authors.lastname: Liljeström
authors.forename: Jari
authors.initials: J
authors.lastname: Salo
authors.forename: Seppo
authors.initials: S
authors.lastname: Santavirta
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
mesh_terms: D000368:Aged; D019644:Arthroplasty, Replacement, Hip; D002117:Calcitriol / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D056657:Cathepsin K; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry; D016207:Cytokines / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006622:Hip Prosthesis; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D010014:Osteolysis / Q000378:metabolism / Q000473:pathology; D053244:Osteoprotegerin; D011475:Prosthesis Failure; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D016207:Cytokines; 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; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K; D002117:Calcitriol