| Autor: |
Ma, Guofeng, Ainola, Mari, Liljeström, Mikko, Santavirta, Seppo, Poduval, Praseet, Zhao, Desheng, Chen, Tong, Konttinen, Yrjö |
| Zdroj: |
Journal of Rheumatology; October 2005, Vol. 32 Issue: 10 p1943-19501950, 19500008p |
| Abstrakt: |
OBJECTIVE: To assess the expression and processing of a disintegrin and metalloproteinase, ADAM 12 (meltrin-a), in the formation of multinuclear cells. Methods. In situ hybridization, immunohistochemical staining, and Western blotting of interface membrane around loosened total hip replacement implants. Macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor-kB ligand (RANKL) costimulation of human monocytes followed by FACS, immunofluorescence staining, Western blotting, and bone resorption assay. RESULTS: ADAM 12 mRNA-containing mononuclear cells were often seen in a close spatial relationship with ADAM 12-positive multinuclear cells. Morphometric analysis of ADAM 12 disclosed that 53% ± 2% of all interface cells were ADAM 12-positive compared to 5% ± 1% in controls (p < 0.001). M-CSF and RANKL were richly present in interface tissue around loosening implants. Upon M-CSF and RANKL costimulation of human monocytes in vitro, the ADAM 12 staining pattern changed over time, and ADAM 12-positive cells formed large mono-, bi-, and multinuclear cells at Day 7 and many multinuclear giant cells and/or osteoclasts at Day 14. Western blot disclosed 90 kDa latent ADAM 12L but also the metalloproteinase-cleaved, fusion-active 60 kDa form transiently just before the burst of fusion. CONCLUSION: ADAM 12, well recognized for participation in cell–cell fusion in myoblast formation, is upregulated and processed upon formation of multinuclear giant cells and osteoclasts. It may play a role in formation of giant cells and osteoclasts around loosened total hip replacement implants. |
| Databáze: |
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