Cartilage Matrix Depletion by Rheumatoid Synovial Cells in Tissue Culture

Abstract

In chronic rheumatoid arthritis, the synovial membrane grows as a pannus over the articular cartilage and erodes it, producing irreversible changes in joint structure and function. On the basis of many experimental observations, hydrolytic enzymes from various sources in the rheumatoid joint have been thought to contribute to the dissolution of the cartilage matrix.Barnett (1) showed that when hyaluronidase was injected into a rabbit joint which was then vigorously exercised, there was a loss of articular cartilage ground substance, presumably due to digestion of the polysaccharide chains of the protein-polysaccharide (PP) of the matrix. Since Dingle (2) first proposed that lysosomal enzymes might degrade the matrix of articular cartilage in the rheumatoid joint, considerable indirect evidence has accumulated to support this suggestion. Some of the evidence and literature citations are presented elsewhere (3, 4) and are briefly summarized here. The rheumatoid synovial membrane contains a much higher content of lysosomal enzymes than the normal membrane, as revealed by cytochemical stains using the light and electron microscope, and by chemical analyses of enzyme activities in homogenates. High levels of lysosomal enzymes are present in rheumatoid synovial fluids and presumably arise either from dissolution of leukocytes in the fluid, or from lining cells in the synovial membrane, or from both. Extracts of rheumatoid, but not normal, synovial membrane and preparations of lysosomal enzymes obtained from liver degrade viscous solutions of the ground substance extracted from cartilage matrix. Injection into rabbit joints of streptolysin S, which is thought to "labilize" lysosomal enzymes, causes a proliferative synovitis with pannus formation and cartilage erosion.The experimental basis for reversible cartilage matrix depletion by proteolytic enzymes was provided by Thomas (5). He showed that papain injected intravenously into rabbits caused their ears to droop. After several days, the ears returned to their erect position.

The Role of Soft Connective Tissue in the Breakdown of Pig Articular Cartilage Cultivated in the Presence of Complement-Sufficient Antiserum to Pig Erythrocytes

“…Chaplin [1971], describing the macroscopic changes in the knee joint in early rheumatoid arthritis, writes: 'The area of softening seen on the condyles before erosions appear, suggests that the cartilage is damaged before pannus erodes it.' The view that the rheumatoid syn ovium secretes an enzyme, or enzymes, capable of degrading cartilage matrix is supported by the interesting experiments of Hammerman et al [1967], They cultivated synovial cells from both rheumatoid arthritic and non-rheumatoid patients, for several cell generations, then deposited fragments of cartilage on the layers of synovial cells and maintained the cultures for a further 17-19 days. They found that whereas the cartilage in the control cultures showed only minor changes, that in the cultures of rheumatoid synovium was depleted of protein and polysaccharide, al though the cartilage had not been invaded by the synovial cells.…”

Studies on collagenase from rheumatoid synovium in tissue culture

“…Before the work of Gross and his colleagues (3, 4, 16) on the metamorphosing tadpole, attempts to identify a specific animal collagenase operative under these conditions had been uniformly unsuccessful. A variety of preparations having some collagenolytic activity had lytic cleavage of the protein of the protein polysaccharide (20). However, previous attempts to identify a collagenolytic substance in synovial fluid or in extracts of synovial tissue have failed (21).…”

Involvement of prostaglandins from rheumatoid synovium in inhibition of articular cartilage metabolism

“…I t is possible to speculate, howcver, that the erosion or depletion of proteoglycan in the matrix of articular cartilage in this instance and in inflammatory arthritis. particularly in early (non-pannus) rheumatoid disease (26), could be due to prostaglandin-induced inhibition of new matrix synthesis acting in concert with en z y m at i c a I I y -i n d u ce d m a t r i x d e p I e t i o n a n d / o r n o r m a I matrix turnover (27).…”