Artikel
Modulation of dopamine receptors on osteoblasts as a possible therapeutic strategy for inducing bone formation in arthritis
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Autoren
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Laura Salinas Tejedor
- IfADo – Leibniz Research Centre for Working Environment and Human Factors, Neuroimmunology, Dortmund
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Markus Rickert
- Universitätsklinikum Gießen und Marburg, Orthopädie und Orthopädische Chirurgie, Gießen
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Jürgen Steinmeyer
- Universitätsklinikum Gießen und Marburg, Orthopädische Klinik, Labor für Experimentelle Orthopädie, Gießen
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Stefan Rehart
- Agaplesion Markus Krankenhaus, Akademisches Lehrkrankenhaus der Johann Wolfgang Goethe-Universität, Klinik für Orthopädie und Unfallchirurgie, Frankfurt am Main
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Elena Neumann
- Justus-Liebig-Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie und Klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
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Ulrike Harre
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Rheumatologie und Immunologie, Erlangen
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Georg Schett
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Rheumatologie und Immunologie, Erlangen
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Ulf Müller-Ladner
- Justus-Liebig-Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie und Klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
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Silvia Capellino
- IfADo – Leibniz Research Centre for Working Environment and Human Factors, Neuroimmunology, Dortmund
| Veröffentlicht: | 5. Februar 2019 |
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Gliederung
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Background: Either osteoclastic bone resorption or osteoblastic bone formation dysfunction contributes to inflammatory bone disorders including rheumatoid arthritis (RA). Current therapies target osteoclasts to reduce bone degradation, but few treatments have been developed to promote bone protection by acting directly on osteoblasts (OB). Recently, local production of dopamine in inflamed joints of RA was observed. Thus, in this EU-funded project, we aimed to determine the implication of the neurotransmitter dopamine in the bone remodeling process.
Methods: Presence of all dopamine receptors (DR1-DR5) in mouse and human bone paraffin slides was examined by immunohistochemistry and in isolated human osteoblasts by FACS analysis. The influence of DR activation on human osteoblasts was studied in vitro, supplementing the medium with different dopamine agonists (DA) for 24h. Then, supernatants were collected for cytokine quantification and cell lysates for RNA isolation and subsequent, gene expression analysis.
The effect of dopamine on human bone mineralization was evaluated by treating OB with DA for 14 days during differentiation.
Results: All DR were observed in mouse and human bone tissue, especially in the bone remodeling area. Moreover, isolated human OB maintained the presence of DR, which allowed their study in vitro. The activation of DR with DA significantly increased the secretion of proinflammatory cytokines, such as IL6 and CCL2. Preliminary results of gene expression studies showed that osteoprotegerin (OPG) mRNA levels in OB from RA were 2-folds lower than the levels found in OB from OA. Upon DA treatment, OPG gene expression was reduced in OB from OA, and equaled the basal OPG level in RA. Alkaline phosphatase (ALP) gene expression was similar between RA and OA. Additionally, DA treatment altered the production of bone matrix.
Conclusion: DR were found in the bone remodeling area of human and mouse bone tissue and their activation on human osteoblast seems to have a modulatory effect on bone homeostasis. Further experiments are ongoing to determine which DR could be a promising therapeutic target.
