Periodic Reporting for period 1 - DeBoRA (Dopamine and Bone Metabolism in Rheumatoid Arthritis)
Berichtszeitraum: 2016-09-01 bis 2018-08-31
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic joint inflammation, articular bone erosion and consequently joint destruction that can lead to complete loss of function. RA is not simply a disease of the joints but can affect many other organs and cause, for instance, systemic osteoporosis, a loss of bone mass. Nowadays there are many therapeutics available that can significantly reduce the impact of RA. However, bone destruction and osteoporosis still remains an issue for rheumatologists. Therefore, an efficient long-term therapeutic approach to target bone erosion still need to be established.
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.
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.
We analyzed the effects of dopamine on osteoblasts, the bone matrix-producing cells, isolated from the bone of patients affected by rheumatoid arthritis. To understand if the dopaminergic effects on these cells were due to the pathologic condition, we compared the results from RA patients with results obtained from patients affected by osteoarthritis (OA), a degenerative disease of the joints with no systemic osteoporosis. We also investigated the effect of dopamine on osteoclasts, the bone-degrading cells, obtained by differentiation from blood cells of RA patients and of healthy donors.
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.
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.
Taken together, our results suggest that the neurotransmitter dopamine plays a role in bone metabolism in RA patients.
The modulation of dopaminergic pathway could be therefore a promising therapeutic approach to counteract bone erosion.
The modulation of dopaminergic pathway could be therefore a promising therapeutic approach to counteract bone erosion.