The CD44v7/8 Epitope as a Target to Restrain Proliferation of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis

• Published in: The American journal of pathology Vol. 157; no. 6; pp. 2037 - 2044
• Main Authors: Wibulswas, Auragun, Croft, Daniel, Bacarese-Hamilton, Ian, McIntyre, Peter, Genot, Elisabeth, Kramer, Ijsbrand M.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.12.2000; ASIP; American Society for Investigative Pathology
• Subjects: Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - pathology; Biological and medical sciences; Cell Cycle - physiology; Cell Division - drug effects; Cell Division - physiology; Cells, Cultured; Diseases of the osteoarticular system; Epitopes; Fibroblasts - pathology; Humans; Hyaluronan Receptors - analysis; Hyaluronan Receptors - immunology; Hyaluronan Receptors - physiology; Inflammatory joint diseases; Medical sciences; Regular; Synovial Membrane - pathology; Human; Immunohistochemistry; Cell proliferation; Immunopathology; Cell culture; Antigenic determinant; Pathogenesis; Diseases of the osteoarticular system; Cell adhesion molecule; Autoimmune disease; Inflammatory joint disease; In vitro; Pathology; Chronic; Synovial membrane; Rheumatoid arthritis; Molecular biology; Fibroblast; Apoptosis
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)64842-0

CD44 is a receptor for the glycosaminoglycan hyaluronan. It exists in a large range of isoforms because of variability in the pattern of glycosylation (both N- and O-linked) and of multiple splice variants. Human fibroblast-like synoviocytes derived from patients with rheumatoid arthritis express certain CD44 splice variants and we have investigated the functional implications of their expression. We found that the rate of proliferation of fibroblast-like synoviocytes expressing the CD44v7/8 epitope (average doubling time 55 hours. exceeds those obtained from the same synovial specimen but lacking this particular epitope (69 hours). Antibodies against CD44v7/8, but not against other exons, inhibit cell proliferation with concomitant induction of the cell cycle inhibitors GADD45, GADD153 and the cyclin-dependent protein-kinase inhibitors p21Waf/Cip. These data show that expression of CD44v7/8 contributes to the transformed phenotype of fibroblast-like synoviocytes. More importantly, they reveal the presence of a target that might be amenable to pharmacological intervention in the treatment of rheumatoid arthritis.