Pathobiology of the synovium in osteoarthritis
Authors: Smith M. M. 
Published: March 2003

The synovium is a vascularized soft tissue lining the capsule and intra‐articular structures of diarthrodial joints. The synovial intima consists of a discontinuous layer of synovial lining cells supported by a cell‐containing scaffolding of loose extracellular matrix (ECM) or interstitium, composed of collagen (types III, IV, V, VI), proteoglycans and other extracellular proteins such as fibronectin, tenascin, entactin and laminin. The synovium has several functions critical for maintaining normal joint homeostasis. Synovial fluid (SF) and its constituents are produced by this tissue, which also mediates blood/synovial fluid exchanges, such as some nutrition of the surface cartilage chondrocytes and absorption of foreign particles from the synovial cavity. The synovial ECM also provides hydraulic resistance, preventing rapid seepage of SF out of the joint cavity and modifying the exchange of macromolecules and other solutes between the subintimal capillaries and SF.Two main types of synovial cell have been identified. The most common synovial lining cell is the type B or fibroblast‐like synoviocyte (FLS). FLS are characterised by abundant rough endoplasmic reticulum and dendritic processes which form a network over the intimal surface but are also present in the subintima. The highly proliferative FLS are involved in the production of specialised matrix constituents, including hyaluronan, collagens and fibronectin for the intimal interstitium and high molecular weight hyaluronan for the SF, essential for the preservation of high viscosity and low coefficient of friction between the surfaces of articular cartilage of the joint.The type A lining cell or macrophage‐like synoviocytes (MLS) are round, nonfixed, nonproliferative, immunoreactive cells which express MHC II molecules and cathepsins B, D and L. MLS absorb and degrade extracellular matrix constituents, cell debris, microorganisms and antigens in the synovial fluid and intimal matrix and use a system of capillaries and lymphatics to clear the joint of particles. Activated MLS are an abundant source of pro‐inflammatory mediators which can promote resorption of articular cartilage.Changes which occur in the osteoarthritic (OA) synovium are not as visually striking as those which occur in RA joints, however, this does not mean that OA synovium can be legitimately used as a control tissue for RA studies. In early OA, the synovium can appear grossly normal. A degree of synovial villous hypertrophy, fibrosis and a significant low grade inflammation are usually present in this tissue from subjects with OA, with a mild infiltrate composed primarily of lymphocytes and mononuclear cells. The cellularity is generally much less than that seen in RA tissue, however, natural killer cell activity and mast cell levels are increased in OA synovium, often greater than in RA tissue.Advanced OA is often characterised by cartilaginous fragments embedded in the synovium, resulting in more pronounced synovitis. Corresponding increases in several molecular markers have been described, including cytokines (interleukin‐1β, IL‐1β receptor antagonist) and other molecules implicated in cartilage destruction (stromelysin, aggrecanase‐2, inducible nitric oxide synthase, urokinase‐type plasminogen activator). Most of these changes in the pathology of the synovium have been demonstrated in recent years by immunohistological studies on both human synovial tissues and synovia from animals with surgically induced OA.