Periodic Reporting for period 1 - DeBoRA (Dopamine and Bone Metabolism in Rheumatoid Arthritis)
Reporting period: 2016-09-01 to 2018-08-31
Final goal of this project was to establish a therapeutic approach to target bone remodeling in arthritis, thus not only blocking bone erosion caused by osteoclasts, but also inducing new bone formation by osteoblasts, in order to restore bone mass.
While looking for unknown pathways involved in RA bone metabolism, some clinical evidences, together with few experimental studies and our previous results led us to hypothesize an involvement of the neurotransmitter dopamine in bone erosion in RA. Dopamine (DA) is a neurotransmitter (a chemical messenger) of the central nervous system controlling movement, emotion, cognition, and neuroendocrine interactions. Recent evidence supports a key role of dopamine in the modulation of immune response.
Our hypothesis was that dopamine is involved in bone metabolism in RA. Main goal of this project was therefore to characterize the influence of the dopaminergic pathway on bone metabolism in RA and to identify its potential as therapeutic target towards a bone protective agent.
Our results show that both osteoblasts and osteoclasts are able to respond to dopamine, as they possess the required receptors on the cell surface. During RA, the amount of these receptors on the cell surface tends to increase, thus suggesting a direct involvement of the dopaminergic pathway in the disease.
The activation of specific dopaminergic receptors led to a stronger imbalance between bone degradation and new bone formation, thus causing an even stronger bone loss in vitro. A blockade of specific dopaminergic receptors in bone cells could therefore be a promising basis for future treatments against osteoporosis in arthritis patients.
The modulation of dopaminergic pathway could be therefore a promising therapeutic approach to counteract bone erosion.