Correlation Between Expression of CD44 Splice Variant V8-v9 and Invasiveness of Fibroblast-like Synoviocytes in an in Vitro System

Objectives: Rheumatoid arthritis is characterized by inflammation, hyperplasia of the synovial membrane, pannus formation and degradation of cartilage and bone. Fibroblast-like synoviocytes are thought to be involved in the invasion and subsequent degradation of cartilage. Two processes play a role in cellular invasion: cellular migration and degradation of the extracellular matrix. The adhesion molecule CD44 and chemokine receptors are instrumental in migration and invasion. Both components have been reported to play a role in tumour metastasis but also appear to be implicated in the destruction of synovial joints in rheumatoid arthritis. CD44, an ubiquitously expressed receptor for the glycosaminoglycan hyaluronan, contains 9 exons that are alternatively spliced and this gives rise to the expression of multiple splice variants, each exhibiting different functional capacities.

Methods: In this report we describe an analysis of the expression of chemokine receptors and CD44 splice variants in diseased synovial tissues using the Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). We have correlated our findings with the clinical diagnosis of rheumatoid or osteoarthritis, with invasion into the extracellular matrix in vitro, and with the rate of proliferation of fibroblast-like synoviocytes.

Results And Conclusions: We conclude that fibroblast-like synoviocytes from both osteo- and rheumatoid arthritis express a number of different chemokine receptors and CD44-splice variants, but none of these correlate with a particular diagnosis. However, elevated expression of CD44v8-9 was found to correlate negatively with the invasive capacity of fibroblast-like synoviocytes.