Regulation of synovial cell growth by polypeptide growth factors

In vitro, rheumatoid arthritis (RA) synovial cells display several of the characteristics of neoplastic and virally transformed cells. The recent observation that synovial cell cultures, derived from collagenase digests of synovial membranes from RA patients, proliferate in serum-free medium suggests that these cells have the capacity to synthesize those factors essential for their growth. Direct immunocytochemical staining and Western analysis have identified transforming growth factor-beta (TGF-beta) band and basic fibroblast growth factor (FGF) in the cytoplasm of RA and normal synovial cells in long-term culture. Greater amounts of each growth factor were found in RA, as compared with normal synovial cell lysates. Western analysis identified a single TGF-beta band in RA and normal synovial cell lysates. Four bands were identified by Western analysis on RA synovial cell lysates probed with monoclonal antibodies recognizing bFGF, whereas only two bands (which co-migrated with human native recombinant bFGF) were identified in normal cell lysates probed with these antibodies. Gene expression analysis using PCR identified mRNA transcripts encoding TGF-beta 1 and FGF-2 (bFGF), but not TGF-beta 2 in all cell cultures studied. Taken together, these data indicate that cultured synovial cells co-express TGF-beta 1 and multiple isoforms of hFGF. These data further strengthen the concept that both polypeptide growth factors are involved in the regulation of synovial cell growth.