Wear debris stimulates bone-resorbing factor expression in the fibroblasts and osteoblasts

• Published in: Hip international 2011-03, Vol.21 (2), p.231-237
• Main Authors: Fujii, Jiro, Niida, Shumpei, Yasunaga, Yuji, Yamasaki, Akira, Ochi, Mitsuo
• Format: Article
• Language: English
• Subjects: Animals; Bone Resorption - genetics; Bone Resorption - metabolism; Bone Resorption - pathology; Cells, Cultured; Cytokines - biosynthesis; Cytokines - genetics; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Fibroblasts - metabolism; Fibroblasts - ultrastructure; Gene Expression Regulation; Immunohistochemistry; Male; Mice; Microscopy, Electron; Osteoblasts - metabolism; Osteoblasts - ultrastructure; Parietal Bone - metabolism; Parietal Bone - pathology; Real-Time Polymerase Chain Reaction; RNA - genetics
• ISSN: 1120-7000; 1724-6067
• DOI: 10.5301/HIP.2011.7423

Wear debris is believed to cause periprosthetic osteolysis and loosening of total joint arthroplasties. We investigated the wear debris-mediated osteolysis in wild-type mice and macrophage-deficient Csf1op/Csf1op (op/op) mice using high density polyethylene (HDP) particles transplanted on the parietal bone surface. Four weeks after surgery, phagocytosis of the HDP particles by F4/80-positive macrophages and tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts was observed in the normal mice, but not in the macrophage-deficient op/op mice. These results suggest that macrophages are implicated in wear debris-dependent osteoclast formation. However, HDP particles were phagocytosed not only by macrophages but also by F4/80-negative cells in both genotypes of mice. Electron microscopic observation identified these cells as fibroblasts. Cell culture studies demonstrated that fibroblasts cultured with HDP-particles showed upregulation of interleukin-6 (IL-6) expression compared with non-treated fibroblasts. When we examined the gene expression of osteoblasts that belong to the mesenchymal cell lineage as fibroblasts, we found that the expression of not only IL-6 but also interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α) and cyclooxygenase2 (Cox2) were up-regulated by HDP particle-stimulation. These findings suggest the possibility that fibroblasts and osteoblasts are involved in wear debris-mediated osteolysis within the tissue surrounding artificial joints through the production of bone resorbing factors IL-6, IL-1ß, TNF-α, and Cox2.