Synoviocytes synthesize, bind, and respond to basic fibroblast growth factor.
Rheumatoid arthritis (RA) is a systemic disease characterized by the destructive proliferation of synovial tissue. It has been suggested that this proliferative lesion resembles a malignancy. Although polypeptide growth factors have been implicated in malignant cell growth, their role in the pathogenesis of proliferative but non-neoplastic diseases such as RA has not been extensively studied. We tested the hypothesis that the synoviocyte itself may be a source of growth factor activity. We demonstrated that culture supernatants from synoviocytes obtained from patients with RA, osteoarthritis, and traumatic joint disease contain mitogenic activity. This activity has biologic properties identical to those of basic fibroblast growth factor (bFGF). Specifically, the mitogenic activity is synergistic with insulin and binds to heparin-agarose, but elutes with 2.0M NaCl. In addition, synoviocyte extracts contain a peptide with a molecular weight of approximately 16,000, which reacts with antibody specific for bFGF. Cultured synoviocytes express the bFGF gene, express receptors for bFGF, and proliferate in response to bFGF. We conclude that bFGF derived from the synoviocytes themselves may play a role in stimulating their proliferation in an autocrine manner in disease states such as RA.
Melnyk
V O
VO
Department of Medicine, Oregon Health Sciences University, Portland 97201.
Shipley
G D
GD
Sternfeld
M D
MD
Sherman
L
L
Rosenbaum
J T
JT
D001168:Arthritis / Q000378:metabolism* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002847:Chromatography, Agarose; D005346:Fibroblast Growth Factors / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D007596:Joints / Q000293:injuries; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D011956:Receptors, Cell Surface / Q000032:analysis; D017468:Receptors, Fibroblast Growth Factor; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors