Correlation between expression of CD44 splice variant v8-v9 and invasiveness of fibroblast-like synoviocytes in an in vitro system.
OBJECTIVE
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.


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.
Tolboom
T C A
TC
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. T.C.A.Tolboom@LUMC.nl
Huidekoper
A L
AL
Kramer
I M
IM
Pieterman
E
E
Toes
R E M
RE
Huizinga
T W J
TW
D017398:Alternative Splicing / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D010003:Osteoarthritis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms; D022821:RNA Splice Sites; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
C448906:CD44v9 antigen; D017931:DNA Primers; D018960:Hyaluronan Receptors; D020033:Protein Isoforms; D022821:RNA Splice Sites; D019707:Receptors, Chemokine