Adsorption of collagenase to particulate titanium: a possible mechanism for collagenase localization in periprosthetic tissue.
Osteolysis is a central feature of aseptic loosening of orthopaedic joint prostheses. This destructive process is believed to result from phagocytosis of implant wear debris by periprosthetic and synovial macrophages and the subsequent release of proinflammatory mediators, including collagenase. Isolated murine macrophages were cultured in vitro with particulate titanium in order to explore the mechanism of macrophage activation by particulate wear debris. The results, in which the amount of secreted, soluble collagenase in culture supernatants was inversely proportional to titanium concentration, suggested that titanium strongly adsorbed secreted collagenase. This inference was confirmed by direct binding assays in which particulate titanium coated with adsorbed collagenase bound an alkaline phosphatase conjugated anti-collagenase antibody, but not a conjugated anti-IgG antibody. Adsorption of collagenase was not influenced by preincubation of titanium particles with albumin. The adsorbed collagenase remained enzymatically active as indicated by its ability to hydrolyze a synthetic peptide substrate. These results demonstrate that particulate titanium stimulates collagenase production by macrophages and then strongly adsorbs the secreted proinflammatory enzyme. The process of macrophage stimulation, collagenase secretion, and adsorption may represent an important mechanism for localization and concentration of collagenase in periprosthetic and synovial tissue, a mechanism that ultimately triggers bone resorption through osteoclast activation.
Kane
K R
KR
Grand Rapids Orthopaedic Surgery Residency Program, Michigan, USA.
DeHeer
D H
DH
Owens
S R
SR
Beebe
J D
JD
Swanson
A B
AB
D000327:Adsorption; D000595:Amino Acid Sequence; D000818:Animals; D001672:Biocompatible Materials; D002478:Cells, Cultured; D017364:Collagenases / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D004868:Equipment Failure; D005260:Female; D007595:Joint Prosthesis; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D007840:Latex / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010014:Osteolysis; D013379:Substrate Specificity; D013997:Time Factors; D014025:Titanium / Q000494:pharmacology
D001672:Biocompatible Materials; D007840:Latex; D014025:Titanium; D007770:L-Lactate Dehydrogenase; D017364:Collagenases