Stromelysin, gelatinase A and TIMP-1 in prosthetic interface tissue: a role for macrophages in tissue remodelling.
Aseptic loosening of prosthetic components is the most important long-term complication of total joint replacement. To investigate the underlying destructive mechanisms, periprosthetic tissues from both well-fixed and loosened sites from six patients, undergoing surgery for aseptic loosening of knee or hip prostheses, were analysed in detail by immunohistochemical methods for the presence of matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 (TIMP-1). The tissues contained small numbers of cells positive for either collagenase, stromelysin, gelatinase A or TIMP-1; these were randomly distributed, neither specifically next to the bone interface nor to wear particles, and the number of positive cells did not correlate with macroscopic observations at operation. Gelatinase A was co-localized in cells with prolyl-4-hydroxylase, an enzyme involved in collagen synthesis. The predominant cell type in these tissues was shown to be the macrophage by the use of cell marker antibodies. Dual localization was not technically possible but the results strongly suggest that monocyte/macrophages were the primary source of gelatinase A and TIMP-1. Stromelysin was immunolocalized on connective tissue matrix in four patients, and gelatinase A in one patient, and were also observed in tissues in which there was no evidence of cellular synthesis of these enzymes. This suggests that secretion had taken place previously, resulting in enzyme bound to matrix for some time. Taken together, these data indicate that localized focal connective tissue remodelling occurs in periprosthetic tissues from both well fixed and loosened sites.
Hembry
R M
RM
Department of Cell and Molecular Biology, Strangeways Research Laboratory, Cambridge, UK.
Bagga
M R
MR
Reynolds
J J
JJ
Hamblen
D L
DL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D018093:Gelatinases / Q000032:analysis*; D006023:Glycoproteins / Q000032:analysis*; D006621:Hip Joint / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007595:Joint Prosthesis; D007719:Knee Joint / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2; D019278:Matrix Metalloproteinase 3 / Q000032:analysis*; D008666:Metalloendopeptidases / Q000032:analysis*; D008875:Middle Aged; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D019714:Tissue Inhibitor of Metalloproteinases; D018093:Gelatinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2