PMID- 17009257 OWN - NLM STAT- MEDLINE DCOM- 20061124 LR - 20131121 IS - 0004-3591 (Print) IS - 0004-3591 (Linking) VI - 54 IP - 10 DP - 2006 Oct TI - The role of fibroblasts and fibroblast-derived factors in periprosthetic osteolysis. PG - 3221-32 AB - 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. CONCLUSION: 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. FAU - Koreny, Tamas AU - Koreny T AD - Rush University Medical Center, Chicago, Illinois 60612, USA. FAU - Tunyogi-Csapo, Miklos AU - Tunyogi-Csapo M FAU - Gal, Istvan AU - Gal I FAU - Vermes, Csaba AU - Vermes C FAU - Jacobs, Joshua J AU - Jacobs JJ FAU - Glant, Tibor T AU - Glant TT LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Arthritis Rheum JT - Arthritis and rheumatism JID - 0370605 RN - 0 (Culture Media, Conditioned) RN - 0 (Cytokines) RN - 0 (Osteoprotegerin) RN - 0 (RANK Ligand) RN - 0 (RNA, Messenger) RN - 0 (TNFSF11 protein, human) RN - 0 (Vascular Endothelial Growth Factor A) RN - 81627-83-0 (Macrophage Colony-Stimulating Factor) RN - D1JT611TNE (Titanium) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Arthroplasty, Replacement, Knee/*adverse effects MH - Bone Resorption/genetics/metabolism/pathology/physiopathology MH - Cells, Cultured MH - Culture Media, Conditioned/pharmacology MH - Cytokines/genetics/*metabolism MH - Female MH - Fibroblasts/drug effects/*metabolism/*pathology MH - Gene Expression Regulation/drug effects/physiology MH - Humans MH - Knee Prosthesis/*adverse effects MH - Macrophage Colony-Stimulating Factor/genetics/metabolism MH - Male MH - Middle Aged MH - Osteoclasts/drug effects/pathology MH - Osteolysis/*etiology/*metabolism/pathology MH - Osteoprotegerin/genetics/metabolism MH - Phagocytosis MH - RANK Ligand/genetics/metabolism MH - RNA, Messenger/genetics/metabolism MH - Titanium/pharmacology MH - Vascular Endothelial Growth Factor A/genetics/metabolism EDAT- 2006/09/30 09:00 MHDA- 2006/12/09 09:00 CRDT- 2006/09/30 09:00 PHST- 2006/09/30 09:00 [pubmed] PHST- 2006/12/09 09:00 [medline] PHST- 2006/09/30 09:00 [entrez] AID - 10.1002/art.22134 [doi] PST - ppublish SO - Arthritis Rheum. 2006 Oct;54(10):3221-32. doi: 10.1002/art.22134.