Artikel
Dopamine activates bone metabolism in rheumatoid arthritis
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Autoren
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Silvia Capellino
- Leibniz Research Centre for Working Environment and Human Factors, Department of Immunology, Project Group Neuroimmunology, Dortmund
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Elena Schwendich
- Leibniz Research Centre for Working Environment and Human Factors, Department of Immunology, Project Group Neuroimmunology, Dortmund
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Laura Salinas Tejedor
- Leibniz Research Centre for Working Environment and Human Factors, Department of Immunology, Project Group Neuroimmunology, Dortmund
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Gernot Schmitz
- Leibniz Research Centre for Working Environment and Human Factors, Department of Immunology, Project Group Neuroimmunology, Dortmund
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Markus Rickert
- University Hospital of Giessen and Marburg, Department of Orthopaedics and Orthopaedic Surgery, Marburg
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Jürgen Steinmeyer
- University of Giessen, Department of Orthopaedics and Orthopaedic Surgery, Laboratory for Experimental Orthopaedics, Gießen
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Stefan Rehart
- Agaplesion Markus teaching hospital of Johann Wolfgang Goethe-university, Clinic for Orthopedics and Trauma Surgery, Frankfurt/Main
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Styliani Tsiami
- Rheumazentrum Ruhrgebiet, Herne
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Jürgen Braun
- Rheumazentrum Ruhrgebiet, Herne
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Xenofon Baraliakos
- Rheumazentrum Ruhrgebiet, Herne
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Jörg Reinders
- Leibniz Research Centre for Working Environment and Human Factors, Department of Toxicology, Analytical chemistry, Dortmund
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Elena Neumann
- University of Giessen, Kerckhoff Klinik GmbH, Rheumatology and Clinical Immunology, Bad Nauheim
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Ulf Müller-Ladner
- University of Giessen, Kerckhoff Klinik GmbH, Rheumatology and Clinical Immunology, Bad Nauheim
| Veröffentlicht: | 31. August 2022 |
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Gliederung
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Introduction: Rheumatoid arthritis (RA) is associated with bone erosion, which leads to severe disability and low quality of life. Current therapies target osteoclasts to reduce bone degradation, but more treatment options would be required to promote bone protection by acting directly on osteoblasts (OB) and induce bone formation. Recently, local production of dopamine in inflamed joints of RA was observed. Thus, we aimed to determine the implication of the neurotransmitter dopamine in the bone formation in RA.
Methods: Dopamine receptors (DR) presence in bone tissue of RA (n=14) or osteoarthritis (OA, n=14) patients was examined by immunohistochemistry. DR in isolated OB was analyzed by flow cytometry and dopamine content in isolated OB was evaluated by ELISA. Osteoclasts (OC) were differentiated from PBMCs of healthy controls (HC, n=8) and RA (n=9) patients. Influence of dopamine on OB and OC was tested in vitro, supplementing the medium with specific dopamine agonists. Effect of dopamine on mineralization was evaluated by Alizarin red staining. Cytokine release was measured by ELISA. Osteoclastogenesis was evaluated with TRAP staining. OC markers were analyzed via real-time PCR and bone resorption via staining of resorption pits with toluidine blue.
Results: All DR were observed in bone tissue, especially in the bone remodeling area. Isolated OB maintained DR expression and contained dopamine. Activation of D2-like DR significantly increased bone mineralization in RA osteoblasts and did not alter bone resorption. Macrophage migration inhibitory factor (MIF) and RANKL were increased after D2-like DR stimulation in primary osteoblasts but not in activated osteoblasts after mineralization, and no significant differences were observed for IL-6 and IL-8. D2-like DR stimulation increased osteoclastogenesis but did not alter expression of OC markers.
Conclusion: DR were found in the bone remodeling area of human bone tissue and dopamine can be produced by osteoblasts themselves, thus suggesting a local autocrine/paracrine pathway of dopamine in the bone. D2-like DRs are responsible for bone mineralization in osteoblasts from RA patients without a substantial increase of proinflammatory cytokines nor of bone resorption, thus suggesting the targeting of D2-like DR as a promising therapeutic strategy to counteract bone resorption in arthritis.
Disclosures: Nothing to disclose.
