Open AccessThe role of fibroblasts and fibroblast‐derived factors in periprosthetic osteolysis
Author(s) -
Koreny Tamas,
TunyogiCsapó Miklós,
Gál Istvan,
Vermes Csaba,
Jacobs Joshua J.,
Glant Tibor T.
Publication year - 2006
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.22134
Subject(s) - proinflammatory cytokine , rankl , osteoprotegerin , tumor necrosis factor alpha , chemistry , macrophage colony stimulating factor , fibroblast , monocyte , synovial membrane , chemokine , osteoclast , microbiology and biotechnology , cancer research , biology , macrophage , immunology , inflammation , receptor , biochemistry , activator (genetics) , in vitro
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 α (TNFα), monocyte chemoattractant protein 1 (MCP‐1), interleukin‐1β (IL‐1β), 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‐1β, IL‐6, IL‐8, cyclooxygenase 1 (COX‐1), COX‐2, leukemia inhibitory factor 1, transforming growth factor β1 (TGFβ1), and TGFβ receptor type I. In addition, interface membrane fibroblasts expressed RANKL and osteoprotegerin in response to stimulation with conditioned media, TNFα, or IL‐1β. 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.