Macrophage depletion diminishes implant-wear-induced inflammatory osteolysis in a mouse model.
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 1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) 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.
Ren
Weiping
W
Department of Biomedical Engineering, Wayne State University, Detroit, Michigan 48201, USA. wren@med.wayne.edu
Markel
David C
DC
Schwendener
Reto
R
Ding
Yunhong
Y
Wu
Bin
B
Wooley
Paul H
PH
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001862:Bone Resorption / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D004002:Clodronic Acid / Q000008:administration & dosage / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism; D005260:Female; D020007:Implants, Experimental; D007249:Inflammation / Q000473:pathology*; D053583:Interleukin-1beta / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008081:Liposomes / Q000008:administration & dosage / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology*; D008566:Membranes / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D008970:Molecular Weight; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D010014:Osteolysis / Q000473:pathology*; D020959:Polyethylene / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D000071681:Tartrate-Resistant Acid Phosphatase; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053583:Interleukin-1beta; D007527:Isoenzymes; D008081:Liposomes; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D004002:Clodronic Acid; D020959:Polyethylene; D003094:Collagen; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase