{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:54:34Z","timestamp":1790297674739,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2006,9,28]],"date-time":"2006-09-28T00:00:00Z","timestamp":1159401600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2006,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u2010linked immunosorbent assay, Western blot hybridization, and flow cytometry were used to determine fibroblast protein expression. Tartrate\u2010resistant acid phosphatase staining was used to identify multinucleated osteoclast\u2010like cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The most dominant compounds measured in the conditioned media from interface membranes were tumor necrosis factor \u03b1 (TNF\u03b1), monocyte chemoattractant protein 1 (MCP\u20101), interleukin\u20101\u03b2 (IL\u20101\u03b2), IL\u20106, IL\u20108, and vascular endothelial growth factor. Fibroblasts phagocytosed particulate wear debris and responded to cytokine\/chemokine stimulation. The most prominent up\u2010regulated genes and proteins secreted by fibroblasts in response to stimulation were matrix metalloproteinase 1, MCP\u20101, IL\u20101\u03b2, IL\u20106, IL\u20108, cyclooxygenase 1 (COX\u20101), COX\u20102, leukemia inhibitory factor 1, transforming growth factor \u03b21 (TGF\u03b21), and TGF\u03b2 receptor type I. In addition, interface membrane fibroblasts expressed RANKL and osteoprotegerin in response to stimulation with conditioned media, TNF\u03b1, or IL\u20101\u03b2. Stimulated fibroblasts cocultured with bone marrow cells in the presence of macrophage colony\u2010stimulating factor induced osteoclastogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.22134","type":"journal-article","created":{"date-parts":[[2006,9,28]],"date-time":"2006-09-28T17:00:21Z","timestamp":1159462821000},"page":"3221-3232","source":"Crossref","is-referenced-by-count":95,"title":["The role of fibroblasts and fibroblast\u2010derived factors in periprosthetic 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