COMPLEX CD44 SPLICING COMBINATIONS IN SYNOVIAL FIBROBLASTS FROM ARTHRITIC JOINTS

CD44 is a broadly expressed cell surface glycoprotein which is the maj or cell surface receptor for the glycosaminoglycan, hyaluronan. In hum ans, alternative splicing of up to 9 variant exons (v2-v10) into CD44 mRNA, together with posttranslational modification via glycosylation a nd chondroitin sulfate attachment has the potential of generating a la rge number of CD44 isoforms. Insertion of these various exons has the potential to change the functional capacities of the molecule and has implications in disease. We have analyzed CD44 splice variant expressi on in cultured VCAM-1-positive synovial fibroblasts isolated from pati ents with osteo- or rheumatoid arthritis and from normal synovium. Rhe umatoid and osteoarthritic tissue express CD44 splice variants at the cell surface level. At the mRNA level exons v3, v6, v7, v8, v9 and v10 were detected in different splicing combinations. Rheumatoid tissue s howed high expression, osteoarthritic tissues showed great variation. In contrast, non-inflamed tissue showed no splicing events. Our result s indicate that the nature of CD44 splice variant expression may be li nked to the inflammatory state of the synovial joint.