Correlation between expression of CD44 splice variant v8-v9 and invasiveness of fibroblast-like synoviocytes in an in vitro system
T.C.A. Tolboom1, A.L. Huidekoper1, I.M. Kramer2, E. Pieterman1, R.E.M. Toes1, T.W.J. Huizinga1
1Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands; 2European Institute for Chemistry and Biology, Pessac Cedex, France.
ABSTRACT
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.
Key words
Fibroblast-like synoviocytes, CD44, chemokine receptors, rheumatoid arthritis, invasion.
Please address correspondence to: Tanja C.A. Tolboom, Leiden University Medical Center, Department of
Rheumatology, C4-R, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
E-mail: T.C.A.Tolboom@LUMC.nl
Clin Exp Rheumatol 2004; 22: 158-164.
© Copyright Clinical and Experimental
Rheumatology 2004.