Dopamine and Bone Metabolism in Rheumatoid Arthritis

Información del proyecto

DeBoRA

Identificador del acuerdo de subvención: 703165

DOI

10.3030/703165

Proyecto cerrado

Fecha de la firma de la CE 5 Abril 2016

Fecha de inicio 1 Septiembre 2016

Fecha de finalización 31 Agosto 2018

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 171 460,80

Aportación de la UE

€ 171 460,80

Coordinado por

FORSCHUNGSGESELLSCHAFT FUR ARBEITSPHYSIOLOGIE UND ARBEITSSCHUTZ EV
Germany

Objetivo

Rheumatoid arthritis (RA) is associated with local bone erosion and systemic osteoporosis, which leads to severe disability and low quality of life. Although treatment with biologics can reduce bone loss by inhibiting inflammation, biologics are not able to achieve bone repair and some patients do not respond sufficiently to the treatment. Therefore, an efficient long-term therapeutic approach to target bone erosion and osteopenia still need to be established. Here, we describe a possible involvement of the neurotransmitter dopamine (DA) in bone metabolism and how we aim to use this new pathway to control bone erosion and restore bone mass in RA.

The involvement of DA on joint inflammation in RA was demonstrated in vitro and in vivo, and an elevated concentration of DA in the synovial fluid of RA patients was also described. Moreover, we recently described that DA is produced in RA synovial tissue and can act in an autocrine/paracrine manner. However, it is still unclear which role local DA can exert on bone erosion in RA. We performed preliminary experiments and could confirm the presence of DRs in RA bone remodeling zone and in osteoblasts isolated from RA. Moreover, DR activation stimulated IL-6. This confirms the active role of local DA also on bone metabolism in RA.

Goal of the present study is therefore to elucidate the mechanisms of action of DA in bone remodeling in RA, in order to find out how to modulate this pathway to control bone erosion and stimulate bone formation in RA. Specifically, we will address the following issues: 1) To identify the mechanisms responsible for DRs expression in RA bone remodeling zone, 2) To define mechanisms of action of DRs on bone metabolism in the context of RA 3) To prove the clinical applicability of DA modulation in arthritic joints towards an anti-inflammatory and bone-protective path. Final goal of this project is to establish a new therapeutic approach to block bone erosion and restore bone mass in RA.

Ámbito científico (EuroSciVoc)

• ciencias naturales › ciencias biológicas › neurobiología
• ciencias médicas y de la salud › medicina clínica › reumatología
• ciencias médicas y de la salud › medicina básica › inmunología › enfermedades autoinmunitarias

Programa(s)

• H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions PROGRAMA PRINCIPAL
  
• H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
  

Tema(s)

• MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF)
  

Régimen de financiación

MSCA-IF-EF-RI - RI – Reintegration panel

Convocatoria de propuestas

H2020-MSCA-IF-2015

Coordinador

FORSCHUNGSGESELLSCHAFT FUR ARBEITSPHYSIOLOGIE UND ARBEITSSCHUTZ EV

• Aportación neta de la UEn: € 171 460,80
• Dirección: ARDEYSTRASSE 67 ; 44139 Dortmund ; Alemania
• Región: Nordrhein-Westfalen › Arnsberg › Dortmund, Kreisfreie Stadt
• Tipo de actividad: Higher or Secondary Education Establishments
• Coste total: € 171 460,80