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Modulation of Dopamine Receptors on Osteoblasts as a Possible Therapeutic Strategy for Inducing Bone Formation in Arthritis

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Project Group Neuroimmunology, Department of Immunology, IfADo—Leibniz Research Center for Working Environment and Human Factors, 44139 Dortmund, Germany
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Department of Orthopaedics and Orthopaedic Surgery, University Hospital Giessen and Marburg (UKGM), 35392 Giessen, Germany
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Laboratory for Experimental Orthopaedics, Department of Orthopaedics and Orthopaedic Surgery, Justus Liebig University Giessen, 35392 Giessen, Germany
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Clinic for Orthopedics and Trauma Surgery, Agaplesion Markus Teaching Hospital of Johann Wolfgang Goethe-University, 60431 Frankfurt am Main, Germany
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Rheumazentrum Ruhrgebiet Herne, Ruhr University Bochum, Claudiusstr. 45, 44649 Herne, Germany
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Analytical Chemistry, Department of Toxicology, IfADo—Leibniz Research Center for Working Environment and Human Factors, 44139 Dortmund, Germany
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Kerckhoff-Klinik GmbH, Rheumatology and Clinical Immunology, Justus Liebig University Giessen, 61231 Bad Nauheim, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Daniel Bouvard
Cells 2022, 11(10), 1609; https://doi.org/10.3390/cells11101609
Received: 13 April 2022 / Revised: 29 April 2022 / Accepted: 9 May 2022 / Published: 11 May 2022
(This article belongs to the Section Tissues and Organs)
Rheumatoid arthritis (RA) is associated with systemic osteoporosis, 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). Recently, the local production of dopamine in inflamed joints of RA has been observed. Thus, in this project, we aimed to determine the implication of the neurotransmitter dopamine in the bone formation process in RA. Dopamine receptors (DR) in the human bone tissue of RA or osteoarthritis (OA) patients were examined by immunohistochemistry. DR in isolated human osteoblasts (OB) was analyzed by flow cytometry, and dopamine content was evaluated by ELISA. Osteoclasts (OC) were differentiated from the PBMCs of healthy controls (HC) and RA patients. Isolated cells were treated with specific dopamine agonists. The effect of dopamine on mineralization was evaluated by Alizarin red staining. Cytokine release in supernatants 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. All DR were observed in bone tissue, especially in the bone remodeling area. Isolated OB maintained DR expression, which allowed their study in vitro. Isolated OB expressed tyrosine hydroxylase, the rate-limiting enzyme for dopamine production, and contained dopamine. The activation of D2-like DR significantly increased bone mineralization in RA osteoblasts and increased osteoclastogenesis but did not alter the expression of OC markers nor bone resorption. 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 an increase in bone resorption, thus suggesting the D2-like DR pathway as a possible future therapeutic target to counteract bone resorption in arthritis. View Full-Text
Keywords: rheumatoid arthritis; dopamine; osteoblast; osteoclasts; mineralization rheumatoid arthritis; dopamine; osteoblast; osteoclasts; mineralization
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MDPI and ACS Style

Schwendich, E.; Salinas Tejedor, L.; Schmitz, G.; Rickert, M.; Steinmeyer, J.; Rehart, S.; Tsiami, S.; Braun, J.; Baraliakos, X.; Reinders, J.; Neumann, E.; Müller-Ladner, U.; Capellino, S. Modulation of Dopamine Receptors on Osteoblasts as a Possible Therapeutic Strategy for Inducing Bone Formation in Arthritis. Cells 2022, 11, 1609. https://doi.org/10.3390/cells11101609

AMA Style

Schwendich E, Salinas Tejedor L, Schmitz G, Rickert M, Steinmeyer J, Rehart S, Tsiami S, Braun J, Baraliakos X, Reinders J, Neumann E, Müller-Ladner U, Capellino S. Modulation of Dopamine Receptors on Osteoblasts as a Possible Therapeutic Strategy for Inducing Bone Formation in Arthritis. Cells. 2022; 11(10):1609. https://doi.org/10.3390/cells11101609

Chicago/Turabian Style

Schwendich, Elena, Laura Salinas Tejedor, Gernot Schmitz, Markus Rickert, Jürgen Steinmeyer, Stefan Rehart, Styliani Tsiami, Jürgen Braun, Xenofon Baraliakos, Jörg Reinders, Elena Neumann, Ulf Müller-Ladner, and Silvia Capellino. 2022. "Modulation of Dopamine Receptors on Osteoblasts as a Possible Therapeutic Strategy for Inducing Bone Formation in Arthritis" Cells 11, no. 10: 1609. https://doi.org/10.3390/cells11101609

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