The role of fibroblasts and fibroblast-derived factors in periprosthetic osteolysis

Tamas Koreny, Miklós Tunyogi-Csapó, Istvan Gál, Csaba Vermes, Joshua J. Jacobs, Tibor T. Glant

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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.

Original languageEnglish
Pages (from-to)3221-3232
Number of pages12
JournalArthritis and rheumatism
Volume54
Issue number10
DOIs
Publication statusPublished - Oct 1 2006

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

Koreny, T., Tunyogi-Csapó, M., Gál, I., Vermes, C., Jacobs, J. J., & Glant, T. T. (2006). The role of fibroblasts and fibroblast-derived factors in periprosthetic osteolysis. Arthritis and rheumatism, 54(10), 3221-3232. https://doi.org/10.1002/art.22134