REGULATION OF SYNOVIAL CELL-GROWTH - COEXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA AND BASIC FIBROBLAST GROWTH-FACTOR BY CULTURED SYNOVIAL-CELLS

Objective. To demonstrate expression of transforming growth factor beta (TGFbeta) and basic fibroblast growth factor (bFGF) by cultured rheumatoid arthritis (RA) synovial cells and to investigate their role as synovial cell mitogens. Methods. Polypeptide growth factors were detected and identified by immunocytochemical staining and Western blot analysis. Messenger RNA (mRNA) transcripts encoding TGFbeta and bFGF were identified by polymerase chain reaction analysis. The influence of neutralizing growth factor monoclonal antibodies (MAb) on RA synovial cell growth was investigated. TGFbeta bioactivity was determined by Mv1Lu assay. Results. Lysates of RA, as compared with normal, synovial cells contained greater amounts of TGFbeta and bFGF. Western blot analysis identified a single TGFbeta band (MW approximately 25 kd) in each of the cell lysates examined. Western blot analysis using MAb DE6 identified a doublet of bFGF bands (MW approximately 18.0 kd) in normal synovial cell lysates and 4 bFGF bands (MW approximately 18.0, 22.0, 22.6, and 25.2 kd) in RA synovial cell lysates. RA and normal synovial cells expressed mRNA transcripts encoding TGFbeta1 but not TGFbeta2, and FGF-2 (basic FGF). Additional mRNA transcripts encoding FGF-5 and FGF-7 were expressed by RA, but not normal, synovial cells in culture. In contrast to MAb 1D11.16, which caused a dose-dependent decrease in RA synovial cell growth, MAb DG2 (up to 100 mug/ml) had no effect on cell growth. Conclusion. RA and normal synovial cells cultured in serum-free medium express TGFbeta1 and native bFGF. However, only RA synovial cells in culture express higher molecular weight isoforms of bFGF. TGFbeta1 appears to regulate synovial cell growth in vitro through an external autocrine loop. Despite expression of high-affinity bFGF receptors on cultured synovial cells, the mechanisms by which bFGF modulates synovial cell growth are unknown.