Platelet-derived growth factors and heparin-binding (fibroblast) growth factors in the synovial tissue pathology of rheumatoid arthritis

Abstract

The pathology of rheumatoid arthritis (RA) is characterized by massive tumorlike hyperplasia of synovial connective tissues. Fibroblastlike cells and microvascular endothelial cells are the predominant cell types present in this invasive tissue, particularly at sites of bone erosions. Identification of growth factors or cytokines that drive this process is an important goal of current research. Here we review evidence that platelet-derived growth factor (PDGF)-like and heparin-binding fibroblast growth factor (HBGF)-like polypeptides play a significant role in this process. For example, messenger RNA transcripts for PDGF-A, PDGF-B, HBGF-1, and HBGF-2 are present in RA synovial tissue specimens, and immunoreactive PDGF-like and HBGF-1- and -2-like polypeptides are present in RA synovia. Levels of expression are significantly higher in RA synovia than in osteoarthritis (OA) synovia, and their expression correlates with the extent and intensity of mononuclear cell infiltration. Similarly, PDGF-receptor expression is elevated in RA synovia compared with OA synovia. High levels of tyrosine phosphorylation and Fos and Myc expression are also characteristic of RA synovia and occur in cells after PDGF- and HBGF-receptor interaction. These and other observations strongly support the view that PDGF-like and HBGF-like factors are involved in stimulating the proliferative and invasive phenotype of RA synovial connective tissue cells.