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. 1999 Nov;58(11):683–690. doi: 10.1136/ard.58.11.683

Expression of laminins and their integrin receptors in different conditions of synovial membrane and synovial membrane-like interface tissue

Y Konttinen 1, T F Li 1, J W Xu 1, M Tagaki 1, L Pirila 1, T Silvennoinen 1, S Santavirta 1, I Virtanen 1
PMCID: PMC1752798  PMID: 10531072

Abstract

OBJECTIVE—To demonstrate the expression of laminins (Lns) and their integrin (Int) receptors in different synovial samples and synovial membrane-like interface tissues from well fixed and aseptically loosened total hip replacement (THR), and the potential role of Ln-Int interaction in the production of collagenases and cytokines.
METHODS—Immunohistochemical staining was done to detect the distribution of EHS Ln, Ln α2, α3, α5, β1, β2 chains and Int α1, α2, α3, α6, β1, β4 subunits in different samples. Double immunofluorescence labelling was used to find colocalisation of Int α6 subunit and collagenase-1/collagenase-3/TNFα/IL6.
RESULTS—General Ln immunoreactivity was detected in all specimens. Ln α5, β1 and β2, but not α2 and α3 chains were seen in the synovial lining and the basement membrane of blood vessels with the intensity/extent of labelling in the following rank order: rheumatoid arthritis (RA) loosened prostheses, osteoarthritis, well fixed prostheses, traumatic knees. Among Int subunits, staining for β1 was usually the strongest, followed by staining for Int α6, α1, α3, and α2 subunits, with the same rank order for overall expression of Lns. Int β4 subunit was not detectable in most of the specimens. Double labelling focused on Int α6 subunit disclosed its frequent colocalisation with collagenases 1 and 3 and with tumour necrosis factor α and interleukin 6 in synovial lining.
CONCLUSION—Synovial lining contains Ln-10, Ln-11, and Int α6β1 and α1β1 receptors. In aseptic loosening of THR, interface tissue has a similar Ln subtype and Int receptor composition as RA synovium, which confirms its "lining-like" phenotype. Synovial lining does not contain Ln-5 (α3β3γ2) or Int α6β4, which are components of epithelial hemidesmosomes. The expression of Lns and their Int receptors is upregulated in inflammation. The close spatial relation between Ln and its Int receptors in synovial lining cells containing proteinases and cytokines suggests a potential role in joint destruction and prosthetic loosening.



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Figure 1  .

Figure 1  

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EHS Ln immunoreactivity in synovial membrane and interface tissue. The staining was comparatively strong in the lining layers (arrows), sublining area and basement membrane of blood vessels. Weak staining was occasionally found in deep stroma in the pericellular spaces. The staining in RA synovial membrane was usually the strongest (A), followed by interface tissue from aseptic loosening of THR (B), OA synovial membrane (C), the samples from well fixed THR (D) and the synovial samples from traumatic knees (E). For staining control the specific primary rabbit antiserum to human EHS Ln was replaced with rabbit IgG (F).

Figure 2  .

Figure 2  

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EHS Ln, Ln chains and Int subunits in semi-serial sections of a synovial sample from OA. Panel A: EHS Ln, B: Ln α2 chain, C: Ln α3 chain, D: Ln α5 chain, E: Ln β1 chain, F: Ln β2 chain. Panel G: Int α1 subunit, H: α2 subunit, I: α3 subunit, J: α6 subunit, K: β1 subunit, L: β4 subunit.

Figure 3  .

Figure 3  

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Int α6 subunit staining was intense around the cells in the lining layer and in vascular endothelial cells. Occasionally, weak cellular staining was detected in sublining and deep stroma. Staining was the strongest in RA samples (A), followed by interface tissue from aseptic loosening of THR (B), OA synovial membrane (C), interface tissue from well fixed prostheses (D) and synovial membrane from knee injuries (E). For staining control the primary mouse antihuman Int α6 IgG1 was replaced with monoclonal IgG1 with an irrelevant specificity (F).

Figure 4  .

Figure 4  

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Double immunofluorescence labelling for Int α6 subunit and MMP-1, MMP-13, TNF-α or IL6 in OA. Some of the double positive cells have been marked with arrows. Panel A and B: α6 subunit and MMP-1 double labelling, A: α6 positive cells, B: MMP-1 positive cells; Panel C and D: α6 subunit and MMP-13 double labelling, C: α6 positive cells, D: MMP-13 positive cells; Panel E and F: α6 subunit and TNFα double labelling, E: α6 positive cells, F: TNFα positive cells; Panel G and H: α6 subunit and IL6 double labelling, G: α6 positive cells, H: IL6 positive cells.

Figure 5  .

Figure 5  

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Double immunofluorescence labelling for Int α6 subunit and MMP-1, MMP-13, TNFα or IL6 in synovial membrane-like interface tissues from a patient with aseptic loosening of THR. Panel A and B: α6 subunit and MMP-1 double labelling, A: α6 positive cells, B: MMP-1 positive cells; Panel C and D: α6 subunit and MMP-13 double labelling, C: α6 positive cells, D: MMP-13 positive cells; Panel E and F: α6 subunit and TNFα double labelling, E: α6 positive cells, F: TNFα positive cells; Panel G and H: α6 subunit and IL6 double labelling, G: α6 positive cells, H: IL6 positive cells.

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