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

Objective—To demonstrate the expression of laminins (Lns) and their integrin (Int) receptors in diVerent 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 á2, á3, á5, â1, â2 chains and Int á1, á2, á3, á6, â1, â4 subunits in diVerent samples. Double immunofluorescence labelling was used to find colocalisation of Int á6 subunit and collagenase-1/collagenase3/TNFá/IL6. Results—General Ln immunoreactivity was detected in all specimens. Ln á5, â1 and â2, but not á2 and á3 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 â1 was usually the strongest, followed by staining for Int á6, á1, á3, and á2 subunits, with the same rank order for overall expression of Lns. Int â4 subunit was not detectable in most of the specimens. Double labelling focused on Int á6 subunit disclosed its frequent colocalisation with collagenases 1 and 3 and with tumour necrosis factor á and interleukin 6 in synovial lining. Conclusion—Synovial lining contains Ln10, Ln-11, and Int á6â1 and á1â1 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 (á3â3ã2) or Int á6â4, 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. (Ann Rheum Dis 1999;58:683–690) The formation of synovial membrane-like interface tissue between prostheses/cement and bone is a common pathological finding in aseptic loosening of total hip replacement (THR). The histological features of interface tissue are characteristic of a foreign body granuloma. It presents a similar bone lytic potential as rheumatoid arthritis (RA) synovitis tissue. Most of the previous studies have been focused on the cell reactivity to wear debris and the eVect of bioactive substances secreted by activated cells in periprosthetic osteolysis, whereas little is known about the expression in the interface tissue and potential role of extracellular matrix (ECM) proteins in the process of prostheses loosening. Laminin (Ln) was originally thought to be the third chain of type IV collagen while the resistance to collagenases indicated its noncollagenous nature. To date, five á, three â and two ã chains assembled into 11 diVerent Lns have been clearly identified. Ln network is part of basal lamina and intercellular substance in the synovial lining. The abilities of Lns to stimulate cell adhesion and migration, as well as to influence gene expression, underlie their critical importance in development, diVerentiation and tissue homeostasis. The cell binding to Lns occurs via a variety of cell surface receptors. Integrins are the main way that cells both bind and respond to the ECM. Int á6â1 has been demonstrated to be a major receptor of Lns while the well known collagen receptors, Int á1â1 and á2â1 can also bind to some Lns. The interaction of Lns and their Int receptors can, by influencing the organisation of cytoskeleton, activate intracellular signalling cascades and thus modulate the expression of proteases and cytokines in diVerent tissues and cells. Ann Rheum Dis 1999;58:683–690 683 Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland