Production and Secretion of Gelsolin by Both Human Macrophage- and Fibroblast-like Synoviocytes and GSN Modulation in the Synovial Fluid of Patients with Various Forms of Arthritis.

Abstract

Gelsolin (GSN) is an actin-binding protein involved in cell formation, metabolism and wound closure processes. Since this protein is known to play a role in arthritis, here we investigate how the synovial membrane with its specific synoviocytes contributes to the expression of GSN and how the amount of GSN expressed is modulated by different types of arthritis. Synovial membranes from adult healthy subjects and patients with rheumatoid arthritis (RA) and osteoarthritis (OA) are analyzed by immunofluorescence, Western blot and ELISA. Macrophage-like synoviocytes (MLS) and fibroblast-like synoviocytes (FLS) were isolated, cultured and analyzed for their potential to produce and secrete GSN. In addition, the GSN concentrations in the synovial fluid of various forms of arthritis are determined by ELISA. GSN is produced by the healthy and arthritic synovial membranes. Both forms of synoviocytes (MLS and FLS) release GSN. The results show that there is a significant reduction in GSN in the synovial fluid in adult patients with OA. This reduction is also detectable in adult patients with RA but is not as evident. In juvenile arthritis, there is a slight increase in GSN concentration in the synovial fluid. This study shows that primary MLS and FLS express GSN and that these cells, in addition to articular chondrocytes, contribute to GSN levels in synovial fluid. Furthermore, GSN concentrations are modulated in different types of arthritis. Further studies are needed to fully understand how GSN is involved in joint homeostasis.