title: The role of fibroblasts and fibroblast-derived factors in periprosthetic osteolysis.
abstract: OBJECTIVE
  This study was undertaken to investigate how fibroblasts respond to stimulation with particulate wear debris and/or conditioned media obtained from pathologic tissue, and whether these activated fibroblasts express compounds that are involved in bone resorption.
  
  
  METHODS
  Conditioned media from explant cultures of synovial tissue, periprosthetic soft tissue (interface membranes), titanium particles, and proinflammatory cytokines were used to stimulate fibroblasts. RNase protection assay was used to measure altered gene expression, and enzyme-linked immunosorbent assay, Western blot hybridization, and flow cytometry were used to determine fibroblast protein expression. Tartrate-resistant acid phosphatase staining was used to identify multinucleated osteoclast-like cells.
  
  
  RESULTS
  The most dominant compounds measured in the conditioned media from interface membranes were tumor necrosis factor alpha (TNFalpha), monocyte chemoattractant protein 1 (MCP-1), interleukin-1beta (IL-1beta), IL-6, IL-8, and vascular endothelial growth factor. Fibroblasts phagocytosed particulate wear debris and responded to cytokine/chemokine stimulation. The most prominent up-regulated genes and proteins secreted by fibroblasts in response to stimulation were matrix metalloproteinase 1, MCP-1, IL-1beta, IL-6, IL-8, cyclooxygenase 1 (COX-1), COX-2, leukemia inhibitory factor 1, transforming growth factor beta1 (TGFbeta1), and TGFbeta receptor type I. In addition, interface membrane fibroblasts expressed RANKL and osteoprotegerin in response to stimulation with conditioned media, TNFalpha, or IL-1beta. Stimulated fibroblasts cocultured with bone marrow cells in the presence of macrophage colony-stimulating factor induced osteoclastogenesis.
  
  
  CONCLUSIONS
  Interface membrane fibroblasts respond directly to particulate wear debris, possibly via phagocytosis, expressing proinflammatory cytokines and RANKL. Thus, these cells may be actively involved in osteoclastogenesis and pathologic (periprosthetic) bone resorption.
authors.affiliation: Rush University Medical Center, Chicago, Illinois 60612, USA.
authors.forename: Tamas
authors.initials: T
authors.lastname: Koreny
authors.forename: Miklós
authors.initials: M
authors.lastname: Tunyogi-Csapó
authors.forename: Istvan
authors.initials: I
authors.lastname: Gál
authors.forename: Csaba
authors.initials: C
authors.lastname: Vermes
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Jacobs
authors.forename: Tibor T
authors.initials: TT
authors.lastname: Glant
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D001862:Bone Resorption / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007720:Knee Prosthesis / Q000009:adverse effects*; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D010014:Osteolysis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D010587:Phagocytosis; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014025:Titanium / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; C505688:TNFSF11 protein, human; D042461:Vascular Endothelial Growth Factor A; D016173:Macrophage Colony-Stimulating Factor; D014025:Titanium