Gene expression profile and synovial microcirculation at early stages of collagen-induced arthritis

A better understanding of the initial mechanisms that lead to
arthritic disease could facilitate development of improved
therapeutic strategies. We characterized the synovial
microcirculation of knee joints in susceptible mouse strains
undergoing intradermal immunization with bovine collagen II in
complete Freund's adjuvant to induce arthritis (i.e.
collagen-induced arthritis [ CIA]). Susceptible DBA1/J and collagen
II T-cell receptor transgenic mice were compared with CIA-resistant
FVB/NJ mice. Before onset of clinical symptoms of arthritis, in
vivo fluorescence microscopy of knee joints revealed marked
leucocyte activation and interaction with the endothelial lining of
synovial microvessels. This initial inflammatory cell response
correlated with the gene expression profile at this disease stage.
The majority of the 655 differentially expressed genes belonged to
classes of genes that are involved in cell movement and structure,
cell cycle and signal transduction, as well as transcription,
protein synthesis and metabolism. However, 24 adhesion molecules
and chemokine/cytokine genes were identified, some of which are
known to contribute to arthritis ( e. g. CD44 and neutrophil
cytosolic factor 1) and some of which are novel in this respect (
e. g. CC chemokine ligand-27 and IL-13 receptor alpha(1)). Online
in vivo data on synovial tissue microcirculation, together with
gene expression profiling, emphasize the potential role played by
early inflammatory events in the development of arthritis.