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Macrophage depletion diminishes implant‐wear‐induced inflammatory osteolysis in a mouse model
Author(s) -
Ren Weiping,
Markel David C.,
Schwendener Reto,
Ding Yunhong,
Wu Bin,
Wooley Paul H.
Publication year - 2007
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.31665
Subject(s) - osteolysis , liposome , macrophage , inflammation , calvaria , in vivo , medicine , pathology , materials science , immunology , chemistry , surgery , biology , in vitro , biochemistry , microbiology and biotechnology , nanotechnology
The purpose of this study was to determine whether macrophage depletion using clodronate liposomes diminishes wear‐debris‐induced inflammatory osteolysis in a murine osteolysis model. Ultra high molecular weight polyethylene (UHMWPE) particles were introduced into established air pouches on BALB/c mice, followed by implantation of calvaria bone from syngeneic littermates. Macrophages were depleted by the intraperitoneal injection of clodronate liposome (2 mg) 2 days before bone implantation and re‐injection every 3 days (1 mg) until the sacrifice of the mice. Mice without clodronate liposome therapy or treated with empty liposome as well as mice injected with saline alone were included in this study as controls. Pouch tissues were collected 14 days after bone implantation for molecular and histology analysis. Our findings indicated that (1) macrophage depletion in clodronate‐liposome‐treated mice was achieved, as illustrated by F4/80 immunostaining in both pouch and spleen tissues; (2) clodronate‐liposome treatment significantly reduced UHMWPE‐induced tissue inflammation, with diminished pouch membrane thickness, reduced inflammatory cellular infiltration, and lowered interleukin 1β (IL‐1β) and tumor necrosis factor α (TNFα) expression; (3) clodronate‐liposome treatment markedly reduced the number of TRAP + cells in pouch tissues and protected against bone collagen depletion. In conclusion, this study demonstrates that macrophage depletion using clodronate‐liposome reduces UHMWPE particle‐induced inflammatory osteolysis. This observation supports the hypothesis that macrophages contribute to the severity of UHMWPE particles induced inflammatory osteolysis, and suggest that macrophage depletion represents a viable therapeutic approach to the prevention and treatment of patients with aseptic loosening. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008