C.A.R.E. OA · Cross-linking Adenosine Receptors - Estrogen receptors for OA treatment
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-02-25 → 2023-02-24
- EU contribution
- €203,852
- Participants
- 1
- Scheme
- MSCA-IF
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Results in brief
Cross-linking Adenosine Receptors - Estrogen receptors for OA treatment
Osteoarthritis (OA) is a common rheumatic disease that affects more than 30 million people worldwide, a number that will continue to rise in the coming decades due to the increased life expectancy and increased prevalence of obesity in the population. There is no cure for OA and the treatments to manage the symptoms, pharmacological and non-pharmacological therapies, are useful only for a limited time, after which joint replacement is necessary. Women have an increased risk of developing OA compared to men, and the risk rises after menopause, when the level of the female sex hormone estradiol decreases. Normal joint function is maintained by many different cells and molecules. A molecule that plays an important role in the healthy function of the joint is adenosine. It has been shown that adenosine signaling can be affected by estradiol in certain types of cells, but it is still unclear whether this can happen in T cells, a cell type in the immune system that contributes to increased inflammation in OA. The purpose of the study was to investigate whether estradiol can regulate the function of adenosine in T cells and thus reduce inflammation in the joints, as well as to evaluate whether regulation of estradiol and adenosine interactions can be used as a treatment for OA. The project was implemented following 3 objectives: • Training objective: To enhance professional skills and become a research leader; • Research objective 1: To test the hypothesis that estradiol modulates the expression and function of the adenosine receptors in T cells; • Research objective 2: To determine if combined treatment with estradiol and a modulator of the adenosine signaling reduces the disease progression in an OA mouse model.
Data: CORDIS, © European Union
Project objective
The purpose of this project is to define how estrogen- and adenosine-receptors modulate each other in CD4+ T-cells during osteoarthritis (OA) development and how these pathways can be targeted for development of a new OA therapy. Alterations of the articular cartilage function and of the joint surrounding tissues lead to disease like OA. OA is a chronic invalidating disease with a large social impact. There is no cure and the treatments to manage symptoms, pharmacological and non-pharmacological therapies, are useful only for a limited time, after which joint replacement surgery is necessary. Women have increased risk of developing OA compared to men and epidemiology studies suggest that hormonal alterations play an important role in OA development. It is now widely recognized that inflammation is an important disease mechanism in OA pathogenesis. In particular CD4+ T cells have been identified as triggers of cartilage degradation in OA. CD4+ T cells express estrogen- and adenosine receptors, two important regulators of the immune system. In a recently published article, I showed that female mice lacking one of the adenosine receptors, A2A (A2AR), develop spontaneous OA with significantly milder disease symptoms compared to males suggesting a protective effect of female sex hormones on OA development. Interestingly, it has been shown that estrogens can modulate the expression of adenosine receptors. In this project, I am going to investigate the effect of pharmacological activation of estrogen receptors on the anti-inflammatory A2AR and the pro-inflammatory A2BR, and the involvement of their mutual interaction on CD4+ T cell proliferation, differentiation and migration ability. Moreover, the effect of combined A2B adenosine receptor blocking and estrogen treatment will be tested as a strategy for reducing pain and disease progression in an OA mouse model.
Original text from CORDIS.
Participants
- GOETEBORGS UNIVERSITET · GoeteborgCoordinatorSweden
Links
Data: CORDIS, © European Union