Expression of pleiotrophin, an embryonic growth and differentiation factor, in rheumatoid arthritis

• Published in: Arthritis and rheumatism 2003-03, Vol.48 (3), p.660-667
• Main Authors: Pufe, Thomas, Bartscher, Michaela, Petersen, Wolf, Tillmann, Bernhard, Mentlein, Rolf
• Format: Article
• Language: English
• Subjects: Animals; Arthritis, Rheumatoid - metabolism; Biological and medical sciences; Carrier Proteins - biosynthesis; Carrier Proteins - genetics; Carrier Proteins - pharmacology; Cell Division - drug effects; Cells, Cultured; Cytokines - biosynthesis; Cytokines - genetics; Cytokines - pharmacology; Diseases of the osteoarticular system; DNA Primers - chemistry; Dose-Response Relationship, Drug; Endothelial Growth Factors - biosynthesis; Enzyme-Linked Immunosorbent Assay; Growth Substances - biosynthesis; Growth Substances - genetics; Humans; Immunoenzyme Techniques; Inflammatory joint diseases; Intercellular Signaling Peptides and Proteins - biosynthesis; Lymphokines - biosynthesis; Medical sciences; Monocytes - drug effects; Monocytes - pathology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Skin - drug effects; Skin - pathology; Synovial Membrane - drug effects; Synovial Membrane - metabolism; Synovial Membrane - pathology; Tumor Necrosis Factor-alpha - pharmacology; Up-Regulation; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
• ISSN: 0004-3591; 1529-0131
• DOI: 10.1002/art.10839

Objective Pleiotrophin (PTN), a 15.3‐kd heparin‐binding peptide, is expressed in mesodermal and neuroectodermal cells during development, but rarely in adult tissues. Since developmentally regulated factors often reappear during disease, we sought to determine whether there was PTN expression in the synovial membranes of patients with rheumatoid arthritis (RA). Methods PTN messenger RNA expression was assayed by quantitative reverse transcriptase–polymerase chain reaction. The protein was localized by immunohistochemistry and quantified by enzyme‐linked immunosorbent assay (ELISA). Effects of PTN on cell proliferation in vitro were determined by DNA measurements. Results PTN expression in normal adult synovial membranes and cartilage was barely detectable. However, PTN was strongly up‐regulated in synovial tissues from patients with RA. In contrast, samples from patients with pyogenic arthritis had moderate PTN levels, and those from patients with osteoarthritis had only a slight increase in PTN, as measured by ELISA. In RA patients, PTN was localized primarily in synoviocytes but was also found in endothelial cells of blood vessels. In cultured mouse fibroblasts used as a model, PTN expression was up‐regulated by tumor necrosis factor α and was more weakly up‐regulated by epidermal growth factor. Recombinant PTN stimulated the proliferation of cultured human synoviocytes and the monocyte cell line THP‐1, but not human dermal fibroblasts, in which PTN increased the synthesis of vascular endothelial growth factor. Conclusion In addition to certain types of cancer, the embryonic growth and differentiation factor PTN is expressed in adults with inflammatory diseases, in particular, RA. Proinflammatory cytokines enhance the expression of PTN. Thus, we propose that PTN is a further paracrine angiogenesis and growth factor for synovial cells in RA.