gms | German Medical Science

43. Kongress der Deutschen Gesellschaft für Rheumatologie, 29. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie, 25. Wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie

02.-05. September 2015, Bremen

Catecholaminergic-to-cholinergic transition of sympathetic nerve fibers is stimulated under healthy but not under inflammatory arthritic conditions

Meeting Abstract

  • Hubert Stangl - Universitätsklinikum Regensburg, Klinik und Poliklinik für Innere Medizin I, Rheumatologie und Klinische Immunologie, Regensburg
  • Robert H. Springorum - Orthopädische Klinik für die Universität Regensburg, Asklepios Klinikum Bad Abbach, Orthopädie, Bad Abbach
  • Dominique Muschter - Universitätsklinikum Regensburg, Experimentelle Orthopädie, Zentrum für Medizinische Biotechnologie, Regensburg
  • Susanne Grässel - Universitätsklinikum Regensburg, Experimentelle Orthopädie, Zentrum für Medizinische Biotechnologie, Regensburg
  • Rainer H. Straub - Innere Med I, Universitätsklinikum Regensburg, Regensburg

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. 43. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 29. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 25. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Bremen, 02.-05.09.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. DocER.19

doi: 10.3205/15dgrh073, urn:nbn:de:0183-15dgrh0738

Veröffentlicht: 1. September 2015

© 2015 Stangl et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe



Introduction: Density of sympathetic nerve fibers decreases in inflamed arthritic tissue tested by immunoreactivity towards tyrosine-hydroxylase (TH, catecholaminergic key enzyme). Since sympathetic nerve fibers can change phenotype from catecholaminergic to cholinergic (example: sweat glands, periosteum), an observed loss of sympathetic nerve fibers may relate to undetectable TH. We aimed to investigate possible catecholaminergic-to-cholinergic transition of sympathetic nerve fibers in synovial tissue of animals with arthritis, and patients with rheumatoid arthritis (RA) and osteoarthritis (OA), and we wanted to find a possible transition factor.

Methods: Nerve fibers were detected by immunofluorescence towards TH (catecholaminergic) and vesicular acetylcholine transporter (VAChT, cholinergic). Co-culture experiments with sympathetic ganglia and lymphocytes or osteoclast progenitors were designed to find stimulators of catecholaminergic-to-cholinergic transition (including gene expression and proteome profiling).

Results: In mouse joints, an increased density of cholinergic relative to catecholaminergic nerve fibers appeared towards day 35 after immunization, but most cholinergic nerve fibers were located in healthy joint-adjacent skin or muscle and almost none in inflamed synovial tissue. In humans, cholinergic fibers are more prevalent in OA synovial tissue than in RA. Co-culture of sympathetic ganglia with osteoclast progenitors (OCPs) obtained from healthy but not from arthritic animals induced catecholaminergic-to-cholinergic transition. Osteoclast mRNA microarray data indicated that leukemia inhibitory factor (LIF) is a candidate transition factor in this setup, which was confirmed in ganglia experiments, particularly, in the presence of progesterone. Additionally, extracellular matrix related genes, oncostatin M (OSM, a known transition factor) and tissue inhibitor of metalloproteinase 1 (TIMP-1) protein were elevated in OCPs from healthy mice. In OCPs from arthritic mice, chemokine genes typical for macrophages and CCL5 (chemokine C-C motif ligand 5) protein were upregulated.

Conclusion: In humans and mice, catecholaminergic-to-cholinergic sympathetic transition happens in less inflamed tissue but not in inflamed arthritic tissue. Under healthy conditions, presence of cholinergic sympathetic nerve fibers may support the cholinergic anti-inflammatory influence recently described.