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-1beta,
TNFalpha, 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 (microCT)] 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.