Production of matrix metalloproteinases at the bone-implant interface in loose total hip replacements.
BACKGROUND
Incidence of aseptic loosening of hip prostheses is increasing in recent years. Previous studies suggested involvement of proteinases and cytokines in the accelerated bone lysis associated with loosening.


METHODS
To investigate the role of matrix metalloproteinases (MMPs) in the loosening we immunolocalized MMP-1 (tissue collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin-1), MMP-9 (gelatinase B) and their common inhibitors, tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), in the bone-prosthesis interface membranes. In situ hybridization was performed for the detection of MMP-9 mRNA in the membranes. The amounts of these MMPs and TIMPs in the tissue were measured by the sandwich enzyme immunoassays and enzyme activities assayed using radiolabeled collagen, gelatin, and carboxymethylated transferrin substrates. We also examined the ability of the cells from interface membranes to resorb mouse calvaria bone.


RESULTS
The membranes obtained from the loose bone-implant interface were composed of fibrous granulation tissue containing numerous multinucleated giant cells with high density polyethylene debris. Immunohistochemical examination revealed that the giant cells were strongly positive for MMP-9 and weakly for MMP-1. Expression of MMP-9 mRNA in the cells was demonstrated by in situ hybridization. MMP-2 and TIMP-2 were immunolocalized mainly in the fibroblasts. TIMP-1 was localized in the endothelial cells of the blood vessels and weakly in fibroblasts. However, MMP-3 was almost negative in the membrane tissue. Sandwich enzyme immunoassays showed that MMP-9 levels are significantly higher in both homogenates and culture media of the cup and stem interface membranes than the control pseudocapsule. Gelatinolytic activity was also remarkably higher in the membrane samples than the control. The cells isolated from the membranes had no ability to resorb calvaria bone.


CONCLUSIONS
These data demonstrate that MMP-9 is produced by the multinucleated giant cells appeared by the reaction to polyethylene debris in the interface membranes. This proteinase may play a role in degradation of the extracellular matrix macromolecules present around and on the surface of the bone trabeculae, facilitating the osteoclastic bone resorption.
Yokohama
Y
Y
Department of Orthopedic Surgery, School of Medicine, Kanazawa University, Japan.
Matsumoto
T
T
Hirakawa
M
M
Kuroki
Y
Y
Fujimoto
N
N
Imai
K
K
Okada
Y
Y
D000328:Adult; D000368:Aged; D000818:Animals; D001862:Bone Resorption; D001842:Bone and Bones / Q000378:metabolism*; D017364:Collagenases / Q000096:biosynthesis; D005260:Female; D018093:Gelatinases / Q000096:biosynthesis; D006023:Glycoproteins / Q000096:biosynthesis*; D006622:Hip Prosthesis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D051379:Mice; D008875:Middle Aged; D014176:Protein Biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1