Expression of ADAM9 (meltrin-gamma) around aseptically loosened total hip replacement implants.
OBJECTIVE
To investigate the involvement of a disintegrin and the metalloproteinase ADAM9 (meltrin-gamma) in the formation of multinuclear giant cells and osteoclasts in aseptic loosening of hip replacement implants.


METHODS
We used in situ hybridization, immunohistochemical staining and western blotting of interface membrane surrounding loosened hip implants, macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor kappaB ligand (RANKL) costimulation and polymethyl methacrylate (PMMA) particle stimulation of human monocytes followed by immunofluorescence staining and flow cytometric analysis.


RESULTS
Morphometric analysis revealed that the ADAM9+ area in the revision total hip replacement (THR) interface was larger than in primary THR samples (37.6+/-5.1 vs 5.2+/-0.8%, P=0.002). Double immunofluorescence staining showed that CD68+ interface tissue macrophages and multinuclear giant cells were ADAM9+. ADAM9 mRNA containing mononuclear and multinuclear cells was often seen in a close spatial relationship with other ADAM9+ cells. Western blotting disclosed a 50 kDa ADAM9 band in tissue extracts. Upon M-CSF and RANKL costimulation of human monocytes, the ADAM9 staining pattern changed over time and ADAM9+ cells formed bi- and multinuclear cells. Flow cytometry disclosed that cells of the monocyte/macrophage lineage changed from ADAM9-negative cells into strongly positive cells during a 3-day culture.


CONCLUSIONS
ADAM9 is expressed in interface tissues around aseptically loosened THR implants. ADAM9 may play a role as a fusion molecule in the formation of multinuclear giant cells and osteoclasts from mononuclear precursors in diseases characterized by bone tissue destruction.
Ma
G-F
GF
Department of Medicine/Invärtes Medicin, P.O. Box 700, FIN-00029 Helsinki University Central Hospital, Finland.
Liljeström
M
M
Ainola
M
M
Chen
T
T
Tiainen
V-M
VM
Lappalainen
R
R
Konttinen
Y T
YT
Salo
J
J
D051722:ADAM Proteins / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D019644:Arthroplasty, Replacement, Hip; D001843:Bone Cements / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D015743:Giant Cells, Foreign-Body / Q000378:metabolism; D006622:Hip Prosthesis; D006801:Humans; D007124:Immunoenzyme Techniques; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D019904:Polymethyl Methacrylate / Q000494:pharmacology; D011475:Prosthesis Failure; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology
D001843:Bone Cements; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D016173:Macrophage Colony-Stimulating Factor; D019904:Polymethyl Methacrylate; D051722:ADAM Proteins; C098339:ADAM9 protein, human