Synovial Fibroblast-Like Cells Strongly Express Jun-B and C-Fos Proto-Oncogenes in Rheumatoid- and Osteoarthritis

To identify recently activated cells in the synovial membrane (SM) of patients with rheumatoid arthritis (RA), the in situ expression of the proto-oncogenes jun-B, c-jun, jun-D, and c-fos was assessed by means of immunohistochemistry and in situ hybridization techniques. SM from patients with osteoarthritis (OA) or joint trauma (JT), as well as from normals (No) were used as controls. Numerous cells expressing high levels of jun-B and c-fos were found within lining layer and diffuse infiltrates in the vicinity of inflammatory cells, but only a few in lymphoid follicles and endothelia. The positive cells were spindle-shaped, CD14- and CD3-negative and, in addition, expressed mRNA for collagen alpha 2 (I) and alpha 1 (III), indicating that they were fibroblasts. In control OA, JT, and even No SM, individual fibroblast-like cells stained as strongly as in RA; however, the density of positive cells was substantially lower. In RA SM, fibroblasts, but not lymphocytes or macrophages, appear to undergo in situ activation. Quantitative differences among RA, OA, and JT may be related to different degrees of inflammatory infiltration.