Basement membrane proteins in synovial membrane: Distribution in rheumatoid arthritis and synthesis by fibroblast-like cells

Abstract

Rheumatoid arthritis is a complex disease of unknown origin. In consequence of some immunological reactions, proliferative invading synovial tissue leads to destruction of normal joint architecture. The aim of this study was to investigate qualitative changes in extracellular matrix distribution of proliferating rheumatoid synovium and their cellular origin. Synovial tissues from 57 clinically indicated arthrotomies were investigated with immunofluorescence, using specific antibodies against extracellular matrix proteins in tissue slides and cultured cells, which were also studied for collagen biosynthesis. Results indicated that synovial fibroblast-like cells synthesize and secrete basement membrane proteins laminin and collagen type IV as e.g. endothelial cells or organogenic fibroblasts. Laminin and collagen type IV were specifically demonstrated pericellularly in the hyperplastic lining layer of active rheumatoid synovitis. These findings are discussed with respect to the possible implication of altered cell-matrix interactions in rheumatoid synovial proliferation.

Loss of collagen type IV in rheumatoid synovia and cytokine effect on the collagen type-IV gene expression in fibroblast-like synoviocytes from rheumatoid arthritis

“…This finding is in agreement with immunofluorescence studies showing a collagen type-IV staining in cultured FLS [28]. In vitro, no differences in the baseline gene expression for collagen type IV were observed between RA-FLS and OA-FLS.…”

“…In chronic synovitis, cytokines may induce a degradative phenotype in SLCs [15]. In situ and in vitro studies have shown that fibroblast-like synovial cells (FLSs) synthesize collagen type IV [19,28]. Since collagen type IV is regarded as a major structural component of the basement membrane, we investigated the in situ distribution of this structural protein using immunochemistry in synovia with chronic synovitis from patients with osteoarthritis (OA) and rheumatoid arthritis (RA).…”

“…The concomitant degradation of the normal synovial tissue and the replacement of this tissue by inflammatory cells and fibrous tissue results in joint destruction and loss of function. Potential effectors of this destructive process are synovial lining cells (SLCs), which have been shown to synthesize extracellular matrix proteins [28] and proteolytic enzymes [18]. In chronic synovitis, cytokines may induce a degradative phenotype in SLCs [15].…”

Isolation and characterization of synovial cells from the human temporomandibular joint

“…On the contrary, the synovial membrane has a basement membrane-like structure in synovial lining layer and the synovial lining layer shows an epitheliallike arrangement (23,(40)(41)(42)(43)(44). Several immunohistochemical studies have demonstrated that the synovial lining cells produce the constituents of basement membranes, such as laminin and type IV collagen (40)(41)(42)(43)(44). In the rat TMJ, Nozawa-Inoue et al (44) demonstrated that a discontinuous basement membrane-like structure was present around the synovial type B cells, but not type A cells nor fibroblasts of a sublining layer under electron microscopic investigation.…”

Integrins and their ligands in rheumatoid arthritis

“…Not only the number of laminin receptors but also the production of laminin itself is upregulated in the synovial lining. Besides endothelial cells, SFs produce and secrete laminin, and its deposition at the synovial lining is increased in RA [28]. Along with collagen and fibronectin, laminin promotes adhesion and proliferation of synovial cells and lymphocytes.…”