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.