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Published on: December 3, 2017
Expression of ADAM9 (meltrin-gamma) around aseptically loosened total hip replacement implants
G-F Ma1, M Liljeström, M Ainola
1Department of Medicine/Invärtes Medicin, P.O. Box 700, FIN-00029 Helsinki University Central Hospital, Finland.
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.
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.
Insights
A disintegrin and metalloproteinase domain-9 (ADAM9) is present in tissues around loose hip implants. ADAM9 may facilitate the formation of multinuclear giant cells and osteoclasts, contributing to bone destruction.
Area of Science:
- Biochemistry
- Cell Biology
- Orthopedic Research
Background:
- Aseptic loosening of total hip replacement (THR) implants is a significant clinical challenge.
- The formation of multinuclear giant cells and osteoclasts contributes to bone tissue destruction in aseptic loosening.
Purpose of the Study:
- To investigate the role of a disintegrin and the metalloproteinase ADAM9 (meltrin-gamma) in the formation of multinuclear giant cells and osteoclasts.
- To examine ADAM9 expression in the interface membrane surrounding aseptically loosened THR implants.
Main Methods:
- In situ hybridization, immunohistochemical staining, and Western blotting were used on interface membrane samples from THR revisions.
- Human monocytes were stimulated with macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor kappaB ligand (RANKL), or polymethyl methacrylate (PMMA) particles.
- Immunofluorescence staining and flow cytometry were employed to analyze cell populations and ADAM9 expression.
Main Results:
- The ADAM9-positive area was significantly larger in revision THR interface tissues compared to primary THR samples.
- ADAM9 was expressed in interface tissue macrophages and multinuclear giant cells, and in mononuclear and multinuclear cells in close proximity.
- Monocytes stimulated with M-CSF and RANKL showed altered ADAM9 expression over time, leading to the formation of bi- and multinuclear cells.
Conclusions:
- ADAM9 is expressed in interface tissues surrounding aseptically loosened THR implants.
- ADAM9 may function as a fusion molecule in the development of multinuclear giant cells and osteoclasts.
- ADAM9 plays a potential role in bone tissue destruction associated with aseptic loosening.
