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Generation of Induced-pluripotent Stem Cells Using Fibroblast-like Synoviocytes Isolated from Joints of Rheumatoid Arthritis Patients
Published on: October 16, 2016
Dopamine induces in vitro migration of synovial fibroblast from patients with rheumatoid arthritis
Lina van Nie1, Laura Salinas-Tejedor2, Nicole Dychus2
1Department of Internal Medicine and Rheumatology, Justus-Liebig-University Gießen, Campus Kerckhoff-Klinik, Benekestr. 2-8, 61231, Bad Nauheim, Germany.
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.
Insights
Dopamine signaling influences the migration of synovial fibroblasts in rheumatoid arthritis (RA) and osteoarthritis (OA). Targeting dopamine receptors may offer a new therapeutic strategy for preventing joint damage in arthritis.
Area of Science:
- Rheumatology
- Cell Biology
- Pharmacology
Background:
- Synovial fibroblast (SF) migration into cartilage is a key target for rheumatoid arthritis (RA) therapy.
- Dopamine receptors (DR) are expressed by SF in RA and osteoarthritis (OA).
Purpose of the Study:
- To investigate the effect of dopamine on the mobility of fibroblasts from patients with chronic arthritides.
- To explore the potential of the dopaminergic pathway as a therapeutic target in RA.
Main Methods:
- Obtained synovial tissue and fibroblasts from RA and OA patients.
- Performed immunohistochemistry for DR subtypes, migration and motility assays under DR stimulation.
- Evaluated cytokines via ELISA, DR expression by flow cytometry, and DR activation using xCELLigence real-time analysis.
Main Results:
- All DR subtypes were expressed in the RA invasion zone.
- Dopamine receptor stimulation increased migration and motility of SF in patients ≤75 years old.
- Older RA patients (>75 years) showed lower D1, D2, and D4 DR expression, with unchanged DR activation.
Conclusions:
- Dopamine influences fibroblast migration in arthritis patients.
- The synovial dopaminergic pathway presents a potential therapeutic target to mitigate joint damage in RA.
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