Human synovium releases a factor which stimulates chondrocyte production of PGE and plasminogen activator

Abstract

The mechanisms by which destruction of the tissues (cartilage, tendons, ligaments and bone) of joints affected by rheumatoid arthritis occurs are still poorly understood. Damage to the articular cartilage is a key event in the development of disability and deformity. Until recently it was thought that destruction of cartilage was primarily due to the release of a variety of proteolytic enzymes (collagenase and other neutral proteinases, and possibly lysosomal hydrolases) from the proliferating synovial pannus tissue¹. Little attention has been paid to the involvement of chondrocytes themselves in the destruction of cartilage. Recently Fell and Jubb² have shown that when porcine synovium and cartilage are maintained in the same organ co-culture system, destruction of the cartilage matrix occurs. They suggested that, in addition to inducing direct enzymatic breakdown of cartilage, synovial tissue might release a factor which activates chondrocytes to degrade their surrounding matrix. Steinberg et al.³ have confirmed that synovium and cartilage interact in this way in tissue culture, with breakdown and release of proteoglycans in cartilage. The purpose of our present study was to examine whether this interaction between synovium and cartilage occurs with human tissue and to examine the mechanisms in more detail. We have, therefore, investigated the effects of normal and rheumatoid synovial tissue on chondrocytes derived from human articular cartilage. We find that the culture medium from explants of normal and rheumatoid human synovium contains a factor which stimulates the production of prostaglandin E (PGE) and plasminogen activator by chondrocytes.