Correlation between increased hyaluronan localized in arthritic synovium and the presence of proliferating cells. A role for macrophage‐derived factors

Abstract

Objective. To determine whether the increased levels of circulating hyaluronan seen in patients with arthritis also occur locally.Methods. Biopsy specimens of normal synovium and synovium from patients with various arthropathies were studied using histochemical and immunohistochemical staining procedures, to determine the tissue distribution of hyaluronan and infiltrating cells.Results. Hyaluronan was found in increased concentrations in inflamed tissues, and was co-localized in sites containing Ki-67+ cells. In vitro analyses showed that macrophage-released factors increased hyaluronan production by fibroblasts. Hydrocortisone inhibited this in vitro production of hyaluronan.Conclusion. Edema and swelling seen in inflamed joints may be due to the presence of large amounts of Previously published in abstract form: Wells AF, Lindblad S, Klareskog L, Laurent T: Hyaluronan in normal synovia and in biopsies from rheumatoid arthritis and other rheumatic diseases. Scand J Immunol32:382, 1990.

Effects of hyaluronic acid and basic fibroblast growth factor on motility of chondrocytes and synovial cells in culture

“…Under such conditions, we speculate that chondrocytes and chondrogenic cells undergo directed migration to the site of the cartilage lesion and initiate reparative processes. HA was also found in increased concentrations in in amed tissues (Wells et al 1992). Therefore, synovial cells are also capable of migration in the presence of large amounts of HA.…”

Serum hyaluronan levels increase with the total number of osteoarthritic joints and are strongly associated with the presence of knee and finger osteoarthritis

“…This biomarker increases in the presence of articular synovitis and cartilage damage [6,7]. Inflamed synovium produces more HA locally and secretes it into the synovial fluid [20]. Increasing intra-articular HA is then forced into blood and lymph due to increasing intra-articular pressure [21].…”

Disease control by regulation of P-glycoprotein on lymphocytes in patients with rheumatoid arthritis

“…Fragmented hyaluronan is increased in the RA synovium and synovial fluid [24,25] . The enhanced production of fragmented hyaluronan is due to increased digestion of native hyaluronan, which is increased in inflammatory foci like synovitis by inflammatory cytokines including IL-1β and TNFα [26] and by oxygenderived free radicals [24,25] . Overexpression of Pgp on lymphocytes induced by these stimuli [15,16] , which also play important roles in the disease activity of RA, parallels the activation of lymphocytes.…”