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Open Access Research article

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

Philip Gierer12, Saleh Ibrahim3, Thomas Mittlmeier1, Dirk Koczan3, Steffen Moeller3, Jürgen Landes4, Georg Gradl12 and Brigitte Vollmar1*

Author Affiliations

1 Department of Experimental Surgery, University of Rostock, Rostock, Germany

2 Department of Trauma & Reconstructive Surgery, University of Rostock, Rostock, Germany

3 Institute of Immunology, University of Rostock, Rostock, Germany

4 Department of Surgery, Klinikum Innenstadt, Ludwig Maximilians University, Munich, Germany

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Arthritis Research & Therapy 2005, 7:R868-R876  doi:10.1186/ar1754

Published: 17 May 2005

Abstract

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 α1). 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.