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We investigated the interactions of particulate PMMA or titanium alloy, patient blood monocytes, and periprosthetic tissues using a SCID-hu model of aseptic loosening. Periprosthetic tissues and bone chips obtained at revision surgery for loosening were transplanted into muscles of SCID mice. Peripheral blood monocytes (PBMCs) isolated from the same donors were fluorescently labeled and co-cultured with PMMA or Ti-6Al-4V particles before intraperitoneal injection. Control mice with periprosthetic tissue or non-inflammatory ligament xenografts received naive PBMCs transfusion. Mice were euthanized 2 weeks after PBMC transfusion. The human tissues were well accepted in SCID mice. Transfused fluorescent-labeled PBMCs were markedly accumulated in transplanted periprosthetic tissues. Multinucleated osteoclast-like cells were commonly seen within retrieved xenograft tissue, and focal bone erosions were ubiquitous. Total cell densities and CD68+ cells within the xenograft were significantly increased in mice transfused with PMMA and Ti-provoked PBMCs compared to the naïve PBMC animals ( p < 0.05). Immunohistochemical staining identified much stronger positive IL-1 and TNF stains in xenografts from either PMMA or Ti-stimulated monocytes transfusion groups ( p < 0.05). TRAP+ cells were found around bone chips in both activated-PBMCs groups, although markedly more aggregated TRAP+ cells in the PMMA-challenged group than in the titanium group ( p < 0.05). MicroCT assessment confirmed the significant decrease of bone mineral density in chips interacted with activated-monocytes/osteoclasts. In conclusion, PMMA or titanium particles readily activate peripheral monocytes and promote the cell trafficking to the debris-containing prosthetic tissues. Particles-provoked PBMCs participated in and promoted the local inflammatory process, osteoclastogenesis, and bone resorption. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:781-786, 2011 [ABSTRACT FROM AUTHOR]

Signaling of RANK (receptor activator of nuclear factor kappa B) through its ligand RANKL appears critical in osteolysis associated with aseptic loosening (AL). The purpose of this study was to investigate the role of RANK in a murine osteolysis model developed in RANK knockout (RANK-/-) mice. Ultra high molecular weight polyethylene (UHMWPE) debris was introduced into established air pouches on RANK-/- mice, followed by implantation of calvaria bone from syngeneic littermates. Wild type C57BL/6 (RANK+/+) mice injected with either UHMWPE or saline alone were included in this study. Pouch tissues were collected 14 days after UHMWPE inoculation for molecular and histology analysis. Results showed that UHMWPE stimulation induced strong pouch tissue inflammation in RANK-/- mice, as manifested by inflammatory cellular infiltration, pouch tissue proliferation, and increased gene expression of IL-1β, TNFα, and RANKL. However, the UHMWPE-induced inflammation in RANK-/- mice was not associated with the osteoclastic bone resorption observed in RANK+/+ mice. In RANK+/+ mice subjected to UHMWPE stimulation, a large number of TRAP+ cells were found on the implanted bone surface, where active osteoclastic bone resorption was observed. No TRAP+ cells were found in UHMWPE-containing pouch tissues of RANK-/- mice. Consistent with the lack of osteoclastic activity shown by TRAP staining, no significant UHMWPE particle-induced bone resorption was found in RANK-/- mice. A well preserved bone collagen content (Van Gieson staining) and normal plateau surface contour [microcomputed tomography (µCT)] of implanted bone was observed in RANK-/- mice subjected to UHMWPE stimulation. In conclusion, this study provides the evidence that UHMWPE particles induce strong inflammatory responses, but not associated with osteoclastic bone resorption in RANK-/- mice. This indicates that RANK signaling is essential for UHMWPE particle-induced osteoclastic bone resorption, but does not participate in UHMWPE particle-induced inflammatory response. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1575-1586, 2006 [ABSTRACT FROM AUTHOR]