title: Wear debris stimulates bone-resorbing factor expression in the fibroblasts and osteoblasts.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery, Hiroshima Prefectural Rehabilitation Centre, Hiroshima - Japan. fujii@rehab-hiroshima.gr.jp
authors.forename: Jiro
authors.initials: J
authors.lastname: Fujii
authors.forename: Shumpei
authors.initials: S
authors.lastname: Niida
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yasunaga
authors.forename: Akira
authors.initials: A
authors.lastname: Yamasaki
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Ochi
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D010006:Osteoblasts / Q000378:metabolism* / Q000648:ultrastructure; D010294:Parietal Bone / Q000378:metabolism / Q000473:pathology; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016207:Cytokines; C025940:bone resorption factor; D012313:RNA