Project description
Untangling the interplay between inflammation, oestrogen and immunity in osteoarthritis
Osteoarthritis (OA), the most common form of arthritis, is a chronic degenerative joint disease that affects millions of people. It is characterised by the deterioration of articular cartilage, which cushions the end of the bones in a joint, causing the bones to rub together and wear down over time. Inflammation and the immune system play a role in OA along with hormonal alterations, which put women at an increased risk for the disease. CD4+ T cells of the immune system are linked to cartilage degradation in OA and they express oestrogen and adenosine receptors. There are two types of adenosine receptors, pro-inflammatory and anti-inflammatory, and oestrogen can modulate the expression of both. The EU-funded C.A.R.E. OA project is investigating the combined effect of oestrogen treatment and blocking of pro-inflammatory adenosine receptors as a potential treatment for OA.
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine surgery
- medical and health sciences health sciences public health epidemiology
- medical and health sciences basic medicine immunology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2019
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
405 30 Goeteborg
Sweden
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.