Artikel
The DeBoRA Project: Dopamine Pathway and Bone Metabolism in Arthritis
Suche in Medline nach
Autoren
-
Silvia Capellino
- Justus-Liebig-Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
-
Markus Rickert
- Universitätsklinikum Gießen und Marburg, Orthopädie und Orthopädische Chirurgie, Gießen
-
Jürgen Steinmeyer
- Universitätsklinikum Gießen und Marburg, Orthopädische Klinik, Labor für Experimentelle Orthopädie, Gießen
-
Stefan Rehart
- Agaplesion Markus Krankenhaus, Akademisches Lehrkrankenhaus der Johann Wolfgang Goethe-Universität, Klinik für Orthopädie und Unfallchirurgie, Frankfurt/Main
-
Elena Neumann
- Justus-Liebig-Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
-
Carsten Watzl
- Leibniz-Institut für Arbeitsforschung an der TU Dortmund, Immunologie, Dortmund
-
Ulf Müller-Ladner
- Justus-Liebig-Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
| Veröffentlicht: | 29. August 2016 |
|---|
Gliederung
Text
Background: An efficient long-term therapeutic approach to counteract bone erosion in rheumatoid arthritis (RA) still needs to be established. Here, we describe a possible involvement of the neurotransmitter dopamine (DA) in bone metabolism.
We recently showed that DA is produced in RA synovial tissue and can act in an autocrine/paracrine manner, but it is still unclear which role local DA can exert on bone erosion in RA. The aim of this EU-funded project is therefore to elucidate the mechanisms of action of DA in bone remodeling in arthritis, in order to find out how to modulate this pathway to control bone erosion.
Methods: Bone tissue was obtained from osteoarthritis (OA, n=6) and RA (n=4) patients during knee joint replacement surgery. Osteoblasts were isolated from the bone spongiosa. Staining of bone samples and of isolated osteoblasts was performed for the five subtypes of DR (D1 to D5). Isolated osteoblasts were treated with specific DR agonists for 24 h. IL-6 and IL-8 were quantified by ELISA. Expression of tyrosine hydroxylase (TH) was quantified by real-time PCR. Mann Whitney test was used for statistical data analysis.
Results: D1, D3 and D4 DR could be detected in the bone remodeling zone of RA patients while OA samples did not express these receptors. D1, D2, D3 and D5 DR were present on isolated osteoblasts, with stronger expression in RA compared to OA. Stimulation of D1-like DR induced a significant dose-dependent increase of IL-6 release in RA compared to control (+79 ±43%, P<0.005). In contrast, no significant effects were detectable for OA osteoblasts. IL-8 release was not significantly altered. TH was expressed in osteoblasts from 5 of 6 OA and from 2 of 4 RA patients, with expression levels even higher than in synovial fibroblasts (up to +50% in RA).
Conclusion: Dopamine receptors are upregulated in the bone remodeling zone of RA patients and their activation seems to have proinflammatory effects and to inhibit osteoblast activation. Expression of TH in osteoblasts suggests autocrine/paracrine effects of dopamine. These data underline the involvement of the dopamine pathway in bone remodeling and joint erosion in RA.
