Particle-induced o
steoly
si
s i
s a major cau
se of a
septic loo
sening after total joint replacement. The po
ssible induction of apopto
si
s ha
s not been addre
ssed in great detail. Thu
s far, it ha
s been
shown that ceramic and polyethylene particle
s can induce apopto
si
s of macrophage
s in vitro. The purpo
se of thi
s study wa
s to te
st the hypothe
si
s that wear
s debri
s generated from total hip arthropla
sty could induce cellular damage and apopto
si
s in vivo. We therefore determined by immunohi
stochemical method
s if increa
sed expre
ssion of p53, an important tran
scription factor, and BAK and Bcl-2, two important regulator
s of apopto
si
s, can be found in interface membrane
s and cap
sule
s of hip
s with a
septically loo
se implant
s.
Strongly positive immunohistochemical staining for p53 and BAK was found in peri-implant tissues from patients with aseptic hip implant loosening. Differentiation of various cell types showed that macrophages stained positive for p53 in all capsule and interface specimens. p53 was frequently detected in giant cells. Positive staining of BAK in macrophages and giant cells was seen in all specimens. Some positive reactions were observed in fibroblasts, only two of 19 cases stained for p53 and three cases for BAK within synovial cells. Positive macrophages and giant cells were localized around polyethylene particles. While T-lymphocytes showed a regular BAK-staining, the other leukocytes were negative. Statistical analyses showed significant positive correlations (style=""text-decoration:none; color:black"" href=""/science?_ob=MathURL&_method=retrieve&_udi=B6TWB-4J5564G-2&_mathId=mml1&_user=10&_cdi=5558&_rdoc=13&_handle=V-WA-A-W-AZ-MsSWYVW-UUA-U-AAVCBCBYEE-AAVWEBVZEE-DBCBWUWZU-AZ-U&_acct=C000050221&_version=1&_userid=10&md5=3f5c8807783c33a2e93288a5cdfe0949"" title=""Click to view the MathML source"">p<0.001) between the presence of polyethylene and metal debris and the expression of BAK and p53. Polyethylene particles were surrounded by more positive macrophages and giant cells than were metal particles, indicating that polyethylene debris may be a stronger inductor of cell cycle arrest and apoptosis than metal debris.
In this study apoptosis of macrophages, giant cells and T-lymphocytes in capsules and interface membranes of patients with aseptic hip implant loosening has been demonstrated in vivo. It is possible that the apoptotic cascade could evolve as a novel therapeutic target to prevent particle-induced osteolysis.