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Rheumatology Advance Access published online on January 17, 2006
Rheumatology, doi:10.1093/rheumatology/kel003
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received July 31, 2005
Accepted December 6, 2005

Original Papers

Expression of ADAM9 (meltrin-{gamma}) around aseptically loosened total hip replacement implants

G.-F. Ma 1, M. Liljeström 2, M. Ainola 2, T. Chen 1, V.-M. Tiainen 3, R. Lappalainen 4, Y. T. Konttinen 5 *, and J. Salo 6

1 Department of Medicine/Invärtes Medicin, Helsinki University Central Hospital, Helsinki
2 Department of Anatomy, Institute of Biomedicine, University of Helsinki, Helsinki
3 ORTON Orthopaedic Hospital of the Invalid Foundation, Helsinki, Helsinki
4 Department of Applied Physics, University of Kuopio, Kuopio, Finland
5 Department of Medicine/Invärtes Medicin, Helsinki University Central Hospital, Helsinki; ORTON Orthopaedic Hospital of the Invalid Foundation, Helsinki, Helsinki; COXA Hospital for Joint Replacement, Tampere
6 Department of Orthopaedics and Traumatology, Helsinki University Central Hospital, Helsinki

* To whom correspondence should be addressed.
Y. T. Konttinen, E-mail: yrjo.konttinen{at}helsinki.fi


  Abstract

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 {kappa}B 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.

Conclusion. 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.

Keywords: ADAM9; Aseptic loosening; Total hip replacement; Multinucleated giant cells; Fusion molecule..
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