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Open Access Research article

Nerve growth factor and receptor expression in rheumatoid arthritis and spondyloarthritis

Christian Barthel1, Nataliya Yeremenko2, Roland Jacobs1, Reinhold E Schmidt1, Michael Bernateck3, Henning Zeidler4, Paul-Peter Tak2, Dominique Baeten2 and Markus Rihl1*

Author Affiliations

1 Clinic for Immunology and Rheumatology, Hannover Medical School (MHH), Carl-Neuberg-Strasse 1, Hannover 30625, Germany

2 Division of Clinical Immunology and Rheumatology, Academic Medical Center (AMC), University of Amsterdam, Meibergdreef 9, Amsterdam, 1105, The Netherlands

3 Department of of Anesthesiology, Pain Clinic, Hannover Medical School (MHH), Carl-Neuberg-Strasse 1, Hannover, 30625, Germany

4 Rheumatologikum Hannover, Rathenaustrasse 13/14, Hannover, 30159, Germany

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Arthritis Research & Therapy 2009, 11:R82  doi:10.1186/ar2716


See related editorial by Forsgren, http://arthritis-research.com/content/11/4/122 and related letter by Raychaudhuri and Raychaudhuri, http://arthritis-research.com/content/12/3/404

Published: 2 June 2009

Abstract

Introduction

We previously described the presence of nerve growth factor receptors in the inflamed synovial compartment. Here we investigated the presence of the corresponding nerve growth factors, with special focus on nerve growth factor (NGF).

Methods

mRNA expression levels of four ligands (NGF, brain derived growth factor (BDNF), neurotrophin (NT)-3, NT-4) and their four corresponding receptors (tyrosine kinase (trk) A, trkB, trkC, NGFRp75) were determined in the synovial fluid (SF) cells of 9 patients with rheumatoid arthritis (RA) and 16 with spondyloarthritis (SpA) and compared with 7 osteoarthritis (OA) patients. NGF was also determined in synovial tissue (ST) biopsies of 10 RA and 10 SpA patients. The production of NGF by monocytes and lymphocytes was assessed by flow cytometry of SF cells, synovial tissue derived fibroblast-like synoviocytes (FLS) were assessed by ELISA on culture supernatant.

Results

SF cell analysis revealed a clear BDNF and NGF mRNA expression, with significantly higher NGF expression in RA and SpA patients than in the OA group. NGF expression was higher in ST samples of RA as compared to SpA. Using intracellular FACS analysis, we could demonstrate the presence of the NGF protein in the two inflammatory arthritis groups on both CD3+ T lymphocytes and CD14+ cells, i.e. monocytes/macrophages, whereas cultured FLS did not produce NGF in vitro.

Conclusions

Neurotrophins and especially NGF are expressed in the synovial fluid and tissue of patients with peripheral synovitis. The presence of neurotrophins as well as their receptors, in particular the NGF/trkA-p75 axis in peripheral synovitis warrants further functional investigation of their active involvement in chronic inflammatory arthritis.