Artikel
Modulation of dopamine receptors as a possible therapeutic strategy for inducing bone formation in Arthritis
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Veröffentlicht: | 4. September 2017 |
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Gliederung
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Background: Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic joint inflammation and systemic osteoporosis. Current therapies target bone resorption, but they do not achieve bone repair. Therefore, a therapeutic strategy that could target osteoblast and promote bone formation is necessary. This EU-funded project aims to determine the role of dopamine (DA) in bone remodeling for identifying a potential therapeutic target that could repair the existing damage.
Methods: Paraffin – embedded bone slides from osteoarthritis (OA), RA patients and from untreated and collagen-induced arthritis (CIA) mice were used for immunohistochemical analysis of dopamine receptors (DR) subtypes. Additionally, human isolated osteoblasts (OB) were cultured in vitro and pre-treated with TNFα for 24h. After medium exchange, DR agonists (Fenoldopam and Ropinirole) were added for additional 24h. IL-6, IL-8, CCL20 and Pro-MMP1 were quantified by ELISA. Tyrosine hydroxylase (TH) expression was measured by RT-PCR.
Results: DR subtypes D1 to D5 were detected in the cartilage/bone interface of RA patients, D3 and D5 receptor were localized in trabecular bone and D1, D3, D4, D5 could be observed in remodeling area of RA patients. DR subtypes D1 and D2 were observed in mouse bone tissue. After isolation, OB maintained DR expression and TH production. Moreover, treatment with D1-like DR agonist promotes the production of IL6, whereas D2-like DR stimulation seemed to increase the synthesis of CCL20 and Pro-MMP1.
Conclusion: Dopamine receptors expression increases during inflammatory conditions in RA osteoblasts and their activation seems to promote bone resorption in an autocrine/paracrine manner.