Mesenchymal cells expressing bone morphogenetic protein receptors are present in the rheumatoid arthritis joint

Objective. To evaluate the presence of cells of an early mesenchymal lineag e, as judged by the expression of bone morphogenetic protein receptors (BMP Rs), in the joints of normal individuals and patients with rheumatoid arthr itis (RA). Methods. Synovial fluids, single cell suspensions of cultured fibroblast-li ke synoviocytes (FLS), and synovial tissues were examined by immunohistolog y with antibodies to BMPR type IA (BMPRIA), BMPRIB, and BMPRII and then qua ntified using computerized image analysis. Other antibodies were evaluated by cytofluorography. Results. In primary cultures of joint effusions from patients with RA and o ther forms of inflammatory arthritis, there were large adherent cells with the appearance of either fibroblasts or stromal cells that stained with ant ibodies to mesenchymal elements-CD44, type I collagen, alpha-actin, and vim entin-but not with antibodies to hematopoietic markers. These cells prolife rated rapidly, expressed BMPRIA and BMPRII, and soon became the predominant cells in culture. They were retained through multiple passages and persist ently displayed surface vascular cell adhesion molecule 1. Immunohistochemi cal analysis of cultured RA FLS (passages 3, 4, and 6; n = 6) revealed that 11.6% were BMPR-positive, while only 2.0% of osteoarthritis BLS (passage 3 ; n = 3) were BMPR-positive, and 1 normal synovial culture had no BMPR-posi tive cells. In all RA synovial membranes examined (n = 9), BMPRI- and BMPRI I-expressing cells were identified in the intimal lining and were also scat tered in the subintima. These cells constituted similar to 25% and similar to 7% of the cells in each area, respectively. Double immunostaining showed no coexpression of BMPR-positive cells with CD68, CD34, or CD3. Cells expr essing BMPR were not seen in any normal synovial samples (n = 4). Strong st aining for BMPR was identified on cells at the invasive front of the pannus and at sites of cartilage erosion. Conclusion. The inflamed RA joint contains BMPR-positive mesenchymal cells. Their origin is still speculative, but since their counterparts in the bon e marrow are essential for osteoclastogenesis, support lymphocyte developme nt and maturation, and protect T cells and B cells from programmed cell dea th, the BMPR-positive cells may be essential elements in the pathogenesis o f RA and other inflammatory forms of chronic synovitis.