Expression of platelet-derived growth factors C and D in the synovial membrane of patients with rheumatoid arthritis and osteoarthritis

Abstract

Objective: To investigate the messenger RNA (mRNA) and protein expression of the recently discovered platelet-derived growth factor C (PDGF-C) and PDGF-D in the synovial membrane (SM) of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to assess the localization and cellular source of these proteins in the SM and their functional influence on synovial fibroblasts.

Methods: Expression of mRNA for PDGFs A, B, C, and D as well as for PDGF receptor (PDGFR) alpha and beta chains in RA and OA SM samples was assessed by real-time reverse transcription-polymerase chain reaction. Protein levels of PDGF-C and PDGF-D were quantified by immunoblotting. Regional and cellular localization of PDGF-C and PDGF-D in the SM was investigated by double-staining immunohistochemistry. In addition, the influence of PDGF-D on the proliferation of synovial fibroblasts and their matrix metalloproteinase (MMP-1) mRNA expression were determined.

Results: The expression of mRNA for PDGFs A, B, and C and for PDGFR alpha and beta chains was comparable in RA and OA SM samples; in contrast, the expression of mRNA for PDGF-D was significantly higher in OA SM. PDGF-C protein was not differentially expressed in OA and RA. The expression of PDGF-D protein was significantly higher in RA SM (full-length and activated form). PDGF-C and PDGF-D were expressed throughout the SM (lining layer, diffuse infiltrates, and stroma) by both synovial fibroblasts and macrophages. In addition, PDGF-D increased the proliferation of synovial fibroblasts and the expression of mRNA for MMP-1.

Conclusion: PDGF-C and PDGF-D are expressed by synovial fibroblasts and macrophages in RA and OA SMs. The levels of PDGF-D protein were significantly higher in RA SM. In addition, PDGF-D stimulated synovial fibroblast proliferation and expression of MMP-1. These findings may have pathogenetic implications for cellular transformation and matrix remodeling in the RA SM.