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Abstract
Preventing synovial fibroblast (SF) migration into the adjacent cartilage is a desirable therapeutic target in rheumatoid arthritis (RA). As previous studies demonstrated that RASF and SF from osteoarthritis (OA) patients express dopamine receptors (DR), aim of the present study was to investigate the impact of dopamine on mobility of fibroblasts from patients with chronic arthritides. Synovial tissue and fibroblasts were obtained from RA and OA patients. Immunohistochemistry was performed for all DR-subtypes in the invasion zone. Migration- and motility-assays were performed under DR-stimulation. Cytokines were evaluated using ELISA. Expression of DRs was evaluated by flow cytometry, and DR activation was measured by xCELLigence real-time analysis. All DRs were expressed in RA invasion zone. Migration and motility of RASF and OASF were increased after DR stimulation in patients ≤ 75 years old. Synovial fibroblasts from older RA patients (> 75 years old) expressed lower levels of D1-, D2- and D4-DR than patients ≤ 75 years old. DR activation was not altered in older patients. Our results suggest a possible involvement of dopamine on migration of fibroblasts from arthritis patients. Therefore, the synovial dopaminergic pathway might represent a potential therapeutic target to interfere with progressive joint damage in RA patients.
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Details
1 Justus-Liebig-University Gießen, Department of Internal Medicine and Rheumatology, Bad Nauheim, Germany (GRID:grid.8664.c) (ISNI:0000 0001 2165 8627)
2 IfADo - Leibniz Research Centre for Working Environment and Human Factors, Department of Immunology, Dortmund, Germany (GRID:grid.419241.b) (ISNI:0000 0001 2285 956X)
3 University of Genoa, Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, Genoa, Italy (GRID:grid.5606.5) (ISNI:0000 0001 2151 3065)
4 Agaplesion Markus Hospital, Department of Orthopedics and Trauma Surgery, Frankfurt, Germany (GRID:grid.491941.0) (ISNI:0000 0004 0621 6785)